Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yusaku Nakabeppu Last modified date:2021.12.09

Professor / Division of Neurofunctional Genoimics / Department of Immunobiology and Neuroscience / Medical Institute of Bioregulation

1. Yukino Miyachi, Takayuki Fujii, Ryo Yamasaki, Daisuke Tsuchimoto, Kyoko Iinuma, Ayako Sakoda, Shoko Fukumoto, Takuya Matsushita, Noriko Isobe, Yusaku Nakabeppu, Jun-ichi Kira, Serum anti-oligodendrocyte autoantibodies in patients with multiple sclerosis detected by a tissue-based immunofluorescence assay, Frontiers in Neurology, 10.3389/fneur.2021.681980, 12, Article 681980, 2021.08, Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical course and disease severity, it is important to identify biomarkers that predict disease activity and severity. In this study, we assessed the frequencies of serum autoantibodies against mature oligodendrocytes in MS patients using a tissue-based immunofluorescence assay (IFA) to determine whether anti-oligodendrocyte antibodies are associated with the clinical features of MS patients and whether they might be a biomarker to assess CNS tissue damage in MS patients. We assessed the binding of serum autoantibodies to mouse oligodendrocytes expressing Nogo-A, a reliable mature oligodendrocyte marker, by IFA with mouse brain and sera from 147 MS patients, comprising 103 relapsing-remitting MS (RRMS), 22 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS) patients, 38 neuromyelitis optica spectrum disorder (NMOSD) patients, and 39 healthy controls (HCs). Western blotting (WB) was performed using extracted mouse cerebellum proteins and IgG from anti-oligodendrocyte antibody-positive MS patients. Tissue-based IFA showed that anti-oligodendrocyte antibodies were positive in 3/22 (13.6%) PPMS and 1/22 (4.5%) SPMS patients but not in RRMS and NMOSD patients or HCs. WB demonstrated the target CNS proteins recognized by serum anti-oligodendrocyte antibodies were approximately 110 kDa and/or 150 kDa. Compared with anti-oligodendrocyte antibody-negative MS patients, MS patients with anti-oligodendrocyte antibodies were significantly older at the time of serum sampling, scored significantly higher on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and had a higher frequency of mental disturbance. Although the clinical significance of anti-oligodendrocyte antibodies is still unclear because of their low frequency, anti-oligodendrocyte autoantibodies are potential biomarkers for monitoring the disease pathology and progression in MS..
2. Mazzei G, Ikegami R, Abolhassani N, Haruyama N, Sakumi K, Saito T, Saido TC, Nakabeppu Y, A high-fat diet exacerbates the Alzheimer’s disease pathology in the hippocampus of the AppNL-F/NL-F knock-in mouse model., Aging Cell, 10.1111/acel.13429, e13429, 2021.07, Insulin resistance and diabetes mellitus are major risk factors for Alzheimer's disease (AD), and studies with transgenic mouse models of AD have provided supportive evidence with some controversies. To overcome potential artifacts derived from transgenes, we used a knock-in mouse model, App(NL-F/NL-F) , which accumulates Abeta plaques from 6 months of age and shows mild cognitive impairment at 18 months of age, without the overproduction of APP. In the present study, 6-month-old male App(NL-F/NL-F) and wild-type mice were fed a regular or high-fat diet (HFD) for 12 months. HFD treatment caused obesity and impaired glucose tolerance (i.e., T2DM conditions) in both wild-type and App(NL-F/NL-F) mice, but only the latter animals exhibited an impaired cognitive function accompanied by marked increases in both Abeta deposition and microgliosis as well as insulin resistance in the hippocampus. Furthermore, HFD-fed App(NL-F/NL-F) mice exhibited a significant decrease in volume of the granule cell layer in the dentate gyrus and an increased accumulation of 8-oxoguanine, an oxidized guanine base, in the nuclei of granule cells. Gene expression profiling by microarrays revealed that the populations of the cell types in hippocampus were not significantly different between the two mouse lines, regardless of the diet. In addition, HFD treatment decreased the expression of the Abeta binding protein transthyretin (TTR) in App(NL-F/NL-F) mice, suggesting that the depletion of TTR underlies the increased Abeta deposition in the hippocampus of HFD-fed App(NL-F/NL-F) mice..
3. Nakamura T, Okabe K, Hirayama S, Chirifu M, Ikemizu S, Morioka H, Nakabeppu Y, Yamagata Y, Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer, Nucleic Acids Res, 10.1093/nar/gkab492, gkab492, 2021.06, Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function..
4. Oka, S., Leon, J., Sakumi, K., Abolhassani, N., Sheng, Z., Tsuchimoto, D., LaFerla, F. M., and Nakabeppu, Y., MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis, Sci Rep, 10.1038/s41598-021-84640-9, 11, 5819, 2021.03, 8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer's disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine in DNA, thereby minimizing 8-oxoG accumulation in DNA. Levels of MTH1 and OGG1 are significantly reduced in the brains of sporadic AD cases. To understand how 8-oxoG accumulation in the genome is involved in AD pathogenesis, we established an AD mouse model with knockout of Mth1 and Ogg1 genes in a 3xTg-AD background. MTH1 and OGG1 deficiency increased 8-oxoG accumulation in nuclear and, to a lesser extent, mitochondrial genomes, causing microglial activation and neuronal loss with impaired cognitive function at 4-5 months of age. Furthermore, minocycline, which inhibits microglial activation and reduces neuroinflammation, markedly decreased the nuclear accumulation of 8-oxoG in microglia, and inhibited microgliosis and neuronal loss. Gene expression profiling revealed that MTH1 and OGG1 efficiently suppress progression of AD by inducing various protective genes against AD pathogenesis initiated by Ass/Tau accumulation in 3xTg-AD brain. Our findings indicate that efficient suppression of 8-oxoG accumulation in brain genomes is a new approach for prevention and treatment of AD..
5. Hu, Y., Yang, C., Amorim, T., Maqbool, M., Lin, J., Li, C., Fang, C., Xue, L., Kwart, A., Fang, H., Yin, M., Janocha, A. J., Tsuchimoto, D., Nakabeppu, Y., Jiang, X., Mejia-Garcia, A., Anwer, F., Khouri, J., Qi, X., Zheng, Q. Y., Yu, J. S., Yan, S., LaFramboise, T., Anderson, K. C., Herlitz, L. C., Munshi, N. C., Lin, J., and Zhao, J., Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury, Cancer Res, 10.1158/0008-5472.CAN-20-1010, 81, 3, 713-723, 2021.02.
6. Sakamoto, H., Miyanishi, K., Tanaka, S., Ito, R., Hamaguchi, K., Sakurada, A., Sato, M., Kubo, T., Osuga, T., Murase, K., Takada, K., Nakabeppu, Y., Kobune, M., and Kato, J., MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model, Sci Rep, 10.1038/s41598-021-83138-8, 11, 1, 3599, 2021.02.
7. Koga, Y., Tsuchimoto, D., Hayashi, Y., Abolhassani, N., Yoneshima, Y., Sakumi, K., Nakanishi, H., Toyokuni, S., and Nakabeppu, Y., Neural stem cell-specific Itpa deficiency causes neural depolarization and epilepsy, JCI Insight , 10.1172/jci.insight.140229, 5, e140229, 2020.11, イノシン三リン酸ピロホスファターゼ(ITPA)は、イノシン三リン酸(ITP)およびその他の脱アミノ化プリンヌクレオシド三リン酸をヌクレオシド一リン酸に加水分解する。近年、ヒトではITPA欠損変異がてんかん発作,小頭症,および発達遅滞を伴う重度の脳症を引き起こすことが報告されてきた。
8. Akamine, S., S. Okuzono, H. Yamamoto, D. Setoyama, N. Sagata, M. Ohgidani, T. A. Kato, T. Ishitani, H. Kato, K. Masuda, Y. Matsushita, H. Ono, Y. Ishizaki, M. Sanefuji, H. Saitsu, N. Matsumoto, D. Kang, S. Kanba, Y. Nakabeppu, Y. Sakai and S. Ohga, GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons, FASEB J , 2020.11.
9. Sun, Q., Chen, J., Xu, L., Kang, J., Wu, X., Ren, Y., Nakabeppu, Y., Wang, Y., and Andrade, J.P., MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model, Oxid Med Cell Longev, 10.1155/2020/4828256, 2020, 4828256, 2020.10.
10. Takashi Ishii, Tatsuhiro Igawa, Hiroshi Hayakawa, Tsugumi Fujita, Mutsuo Sekiguchi M and Yusaku Nakabeppu, PCBP1 and PCBP2 both bind heavily oxidized RNA but cause opposing outcomes, suppressing or increasing apoptosis under oxidative conditions, J Biol Chem, 295, 34, 12247-12261, 2020.08, [URL].
11. Kvandova M., Filippou K., Steven S., Oelze M., Kalinovic S., Stamm P., Frenis K., Vujacic-Mirski K., Sakumi K., Nakabeppu Y., Bagheri Hosseinabadi M., Dovinova I., Epe B., Munzel T., Kroller-Schon S., and Daiber A., Environmental aircraft noise aggravates oxidative DNA damage, granulocyte oxidative burst and nitrate resistance in Ogg1(-/-) mice, Free Radic Res, 10.1080/10715762.2020.1754410, 2020.04.
12. Funahashi S., Okazaki Y., Akatsuka S., Takahashi T., Sakumi K., Nakabeppu Y., and Toyokuni S, Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice, Free Radic Res, 10.1080/10715762.2020.1743285, 54, 2-3, 195-205, 2020.03.
13. Holly Simon, Vladimir Vartanian, Melissa H. Wong, Yusaku Nakabeppu, Priyanka Sharma, R. Stephen Lloyd, Harini Sampath, OGG1 deficiency alters the intestinal microbiome and increases intestinal inflammation in a mouse model, PLoS One, 10.1371/journal.pone.0227501, 15, 1, e0227501, 2020.01, OGG1-deficient (Ogg1-/-) animals display increased propensity to age-induced and diet-induced metabolic diseases, including insulin resistance and fatty liver. Since the intestinal microbiome is increasingly understood to play a role in modulating host metabolic responses, we examined gut microbial composition in Ogg1-/- mice subjected to different nutritional challenges. Interestingly, Ogg1-/- mice had a markedly altered intestinal microbiome under both control-fed and hypercaloric diet conditions. Several microbial species that were increased in Ogg1-/- animals were associated with increased energy harvest, consistent with their propensity to high-fat diet induced weight gain. In addition, several pro-inflammatory microbes were increased in Ogg1-/- mice. Consistent with this observation, Ogg1-/- mice were significantly more sensitive to intestinal inflammation induced by acute exposure to dextran sulfate sodium. Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice..
14. Jingwen Chen, Zhenqian Huang, Xin Wu, Jiaqi Kang, Yan Ren, Wei Gao, Xiang Lu, Jingmei Wang, Weidong Ding, Yusaku Nakabeppu, Yimei Fan, Yaping Wang, Oxidative stress induces different tissue dependent effects on Mutyh-deficient mice, Free Radic Biol Med, 10.1016/j.freeradbiomed.2019.09.005, 143, 482-493, 2019.11, 8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it is generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication is excised by MutY homolog (MUTYH), an important protein of the base excision repair (BER) system. Mutyh plays an important role in the maintenance of genomic integrity, but the functional consequences of Mutyh deficiency are not fully understood. In the current study, we investigated the histological and functional changes of five tissues (hippocampus, heart, liver, kidney and lung) and their molecular basis in Mutyh−/− and wild-type mice exposed to D-galactose (D-gal). Our data indicated that Mutyh deficiency hindered the weight gain of experimental mice and induced substantial alterations of 8-oxoG content and superoxide dismutase (SOD) activity, but no significant histological and functional impairment appeared in the investigated tissues of Mutyh- deficient mice without D-gal exposure. Under low-dose D-gal exposure, Mutyh deficiency altered expression of genes involved in mitochondrial unfolded protein response (UPRmt) in the heart, liver and lung, and caused an enhanced expression of mitochondrial dynamics proteins (MDPs) in hippocampus and liver. The stress responses could maintain mitochondrial proteostasis and function. However, such responses were not noted when experiencing excessive damage burden induced by high-dose D-gal exposure, in which Mutyh deficiency increased accumulation of 8-oxoG and aggravated mitonuclear protein imbalance, as well as histological lesions in heart, liver and kidney. A higher sensitivity to ROS-induced cardiotoxicity with high-dose D-gal exposure was noticed in Mutyh−/− mice. However, no differences in learning and memory impairments were observed between Mutyh−/− and wild-type mice with high-dose D-gal exposure. In conclusion, our data demonstrated that Mutyh deficiency has different impacts on various tissues based on the degree of oxidative stress..
15. Naoki Haruyama, Kunihiko Sakumi, Atsuhisa Katogi, Daisuke Tsuchimoto, Gabriele De Luca, Margherita Bignami, and Yusaku Nakabeppu, 8-Oxoguanine accumulation in aged female brain impairs neurogenesis in the dentate gyrus and major island of Calleja, causing sexually dimorphic phenotypes, Progress in Neurobiology,, 180, 101613, 2019.09, [URL], In mammals, including humans, MTH1 with 8-oxo-dGTPase and OGG1 with 8-oxoguanine DNA glycosylase minimize 8-oxoguanine accumulation in genomic DNA. We investigated age-related alterations in behavior, 8-oxoguanine levels, and neurogenesis in the brains of Mth1/Ogg1-double knockout (TO-DKO), Ogg1-knockout, and human MTH1-transgenic (hMTH1-Tg) mice. Spontaneous locomotor activity was significantly decreased in wild-type mice with age, and females consistently exhibited higher locomotor activity than males. This decrease was significantly suppressed in female but not male TO-DKO mice and markedly enhanced in female hMTH1-Tg mice. Long-term memory retrieval was impaired in middle-aged female TO-DKO mice. 8-Oxoguanine accumulation significantly increased in nuclear DNA, particularly in the dentate gyrus (DG), subventricular zone (SVZ) and major island of Calleja (ICjM) in middle-aged female TO-DKO mice. In middle-aged female TO-DKO mice, neurogenesis was severely impaired in SVZ and DG, accompanied by ICjM and DG atrophy. Conversely, expression of hMTH1 efficiently suppressed 8-oxoguanine accumulation in both SVZ and DG with hypertrophy of ICjM. These findings indicate that newborn neurons from SVZ maintain ICjM in the adult brain, and increased accumulation of 8-oxoguanine in nuclear DNA of neural progenitors in females is caused by 8-oxo-dGTP incorporation during proliferation, causing depletion of neural progenitors, altered behavior, and cognitive function changes with age.
16. Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato, An Intronic Single Nucleotide Polymorphism in the MUTYH Gene Is Associated with Increased Risk for HCV-induced Hepatocellular carcinoma, Free Radic Biol Med, 10.1016/j.freeradbiomed.2018.09.010, 129, 88-96, 2018.12.
17. Takayuki Fujii, Ryo Yamasaki, Kyoko Iinuma, Daisuke Tsuchimoto, Yoshinori Hayashi, Ban-yu Saitoh, Takuya Matsushita, Mizuho A. Kido, Shinichi Aishima, Hiroshi Nakanishi, Yusaku Nakabeppu, Jun-ichi Kira, A novel autoantibody against plexin D1 in patients with neuropathic pain, Ann Neurol, 10.1002/ana.25279, 84, 208-224, 2018.09, [URL].
18. Reiji Hommyo, Satoshi Suzuki, Nona Abolhassani, Hideomi Hamasaki, Masahiro Shijo, Norihisa Maeda, Hiroyuki Honda, Yusaku Nakabeppu, Toru Iwaki, Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis, Neuropathology, 10.1111/neup.12466, 38, 3, 247-259, 2018.06.
19. Hisanao Izumi, Yasuharu Shinoda, Takashi Saito, Takaomi C. Saido, Keita Sato, Yasushi Yabuki, Yotaro Matsumoto, Yoshitomi Kanemitsu, Yoshihisa Tomioka, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga, The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice, Neuroscience, 10.1016/j.neuroscience.2018.02.031, 377, 87-97, 2018.05.
20. Masahiro Shijo, Hiroyuki Honda, Satoshi Suzuki, Hideomi Hamasaki, Masaaki Hokama, Nona Abolhassani, Yusaku Nakabeppu, Toshiharu Ninomiya, Takanari Kitazono, Toru Iwaki, Association of adipocyte enhancer-binding protein 1 with Alzheimer's disease pathology in human hippocampi, Brain Pathology, 10.1111/bpa.12475, 28, 1, 58-71, 2018.01.
21. Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M LaFerla, Yusaku Nakabeppu, Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation, Scientific Reports, 10.1038/s41598-017-17999-3, 7, 1, 17762, 2017.12, Alzheimer’s disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F cortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App NL-G-F/NL-G-F cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD..
22. Guang Hua Li, Shinya Akatsuka, Shan-Hwu Chew, Li Jiang, Takahiro Nishiyama, Akihiko Sakamoto, Takashi Takahashi, Mitsuru Futakuchi, Hiromu Suzuki, Kunihiko Sakumi, Yusaku Nakabeppu, Shinya Toyokuni, Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model, Pathol Int, 10.1111/pin.12598, 67, 11, 564-574, 2017.11.
23. Koji Chikama, HidetakaYamada, TatsuoTsukamoto, Kosuke Kajitani, Yusaku Nakabeppu, Naohisa Uchimura, Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse, Brain Res, 10.1016/j.brainres.2017.09.006, 1676, 77-82, 2017.09.
24. Marco Seifermann, Alexander Ulges, Tobias Bopp, Svetlana Melcea, Andrea Schafer, Sugako Oka, Yusaku Nakabeppu, Arne Klungland, Christof Niehrs, Bernd Epe, Role of the DNA repair glycosylase OGG1 in the activation of murine splenocytes., DNA repair, 10.1016/j.dnarep.2017.08.005, 58, 13-20, 2017.08.
25. Takatoshi Fujishita, Tatsuro Okamoto, Takaki Akamine, Shinkichi Takamori, Kazuki Takada, Masakazu Katsura, Goji Toyokawa, Fumihiro Shoji, Mototsugu Shimokawa, Yoshinao Oda, Yusaku Nakabeppu, Yoshihiko Maehara, Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer., Lung Cancer, 10.1016/j.lungcan.2017.04.012, 109, 52-57, 2017.07.
26. Kosuke Kajitani, Kazuyuki Yanagimoto, Yusaku Nakabeppu, Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation, Psychopharmacology, 10.1007/s00213-017-4683-9, 2017.07.
27. Vladimir Vartanian, Jana Tumova, Pawel Dobrzyn, Yusaku Nakabeppu, R. Stephen Lloyd, Harini Sampath, 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle, PLos One, 10.1371/journal.pone.0181687, 12, 7, e0181687, 2017.07.
28. Shinji Asada, Eiko Ohta, Yoriko Akimoto, ABOLHASSANI NONA, Daisuke Tsuchimoto, Yusaku Nakabeppu, 2-Oxoadenosine induces cytotoxicity through intracellular accumulation of 2-oxo-ATP and depletion of ATP but not via the p38 MAPK pathway, Scientific Reports, 10.1038/s41598-017-06636-8, 7, 1, 6528, 2017.07.
29. Yusuke Yoshii, Taikai Inoue, Yuya Uemura, Yusaku Iwasaki, Toshihiko Yada, Yusaku Nakabeppu, Mami Noda, Complexity of Stomach-Brain Interaction Induced by Molecular Hydrogen in Parkinson's Disease Model Mice, Neurochem Res, 10.1007/s11064-017-2281-1, 2017.05.
30. Chihiro Takemori, Makoto Kunisada, Flandiana Yogianti, Sugako Oka, SAKUMI Kunihiko, Ryusuke Ono, Yusaku Nakabeppu, Chikako Nishigori, Co-regulation of Cxcl1 and versican in the inflammatory response to UVB induced reactive oxygen species in skin photo-tumorigenesis, J Dermatol Sci, 10.1016/j.jdermsci.2016.10.011, 85, 2, 140-143, 2017.02.
31. Shaimaa Waz, Teruya Nakamura, Keisuke Hirata, Yukari Koga Ogawa, Mami Chirifu, Takao Arimori, Taro Tamada, Shinji Ikemizu, Yusaku Nakabeppu, Yuriko Yamagata, Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity, J Biol Chem, 10.1074/jbc.M116.749713, 292, 7, 2785-2794, 2017.02.
32. Nona Abolhassani, Julio Leon, Zijing Sheng, Sugako Oka, Hideomi Hamasaki, Toru Iwaki, Yusaku Nakabeppu, Molecular pathophysiology of impaired glucose metabolism, mitochondrial dysfunction, and oxidative DNA damage in Alzheimer's disease brain, Mech Ageing Dev, 10.1016/j.mad.2016.05.005, 161, 95-104, 2017.01, In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer's disease (AD) research revealed that insulin production and signaling are severely impaired in AD brain, thereby resulting in mitochondrial dysfunction and increased oxidative stress. Among possible oxidative DNA lesions, 8-oxoguanine (8-oxoG) is highly accumulated in the brain of AD patients. Previously we have shown that incorporating 8-oxoG in nuclear and mitochondrial DNA promotes MUTYH (adenine DNA glycosylase) dependent neurodegeneration. Moreover, cortical neurons prepared from MTH1 (8-oxo-dGTPase)/OGG1 (8-oxoG DNA glycosylase)-double deficient adult mouse brains is shown to exhibit significantly poor neuritogenesis in vitro with increased 8-oxoG accumulation in mitochondrial DNA in the absence of antioxidants. Therefore, 8-oxoG can be considered involved in the neurodegenerative process in AD brain. In mild cognitive impairment, mitochondrial dysfunction and oxidative damage may induce synaptic dysfunction due to energy failures in neurons thus resulting in impaired cognitive function. If such abnormality lasts long, it can lead to vicious cycles of oxidative damage, which may then trigger the neurodegenerative process seen in Alzheimer type dementia..
33. Issei Egashira, Fumi Takahashi-Yanaga, Risa Nishida, Masaki Arioka, Kazunobu Igawa, KatsuhikoTomooka, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Takanari Takanari, Toshiyuki Toshiyuki, Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/beta-catenin signaling pathway, Cancer Sci, 10.1111/cas.13106, 108, 1, 108-115, 2017.01.
34. Shingo Akiyama, Hiroshi Saeki, Yuichiro Nakashima, Makoto Imori, Hiroyuki Kitao, Eiji Oki, Yoshinao Oda, Yusaku Nakabeppu, Yoshihiro Kakeji, Yoshihiko Maehara, Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma, Cancer Medicine, 10.1002/cam4.979, 6, 1, 258-266, 2017.01.
35. Michel Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salome Glauzy, Brennan G. Olson, Henner Morbach, Toshiro Ohsumi, Klaus SchmitzAbe, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D. Notarangelo, Eliane Chouery, André Megarbane, Peter B. Kang, Deficiency of the base excision repair enzyme NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies and predisposition to autoimmunity, J Clin Invest, 10.1172/JCI85647., 126, 11, 4219-4236, 2016.11, Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function. Further analysis of the patients revealed an absence of LPS-responsive beige-like anchor (LRBA) protein expression, a known cause of immunodeficiency. We next examined the contribution of NEIL3 to the maintenance of self-tolerance in Neil3-/- mice. Although Neil3-/- mice displayed normal B cell function, they exhibited elevated serum levels of autoantibodies and developed nephritis following treatment with poly(I:C) to mimic microbial stimulation. In Neil3-/- mice, splenic T and B cells as well as germinal center B cells from Peyer's patches showed marked increases in apoptosis and cell death, indicating the potential release of self-antigens that favor autoimmunity. These findings demonstrate that deficiency in NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies, and predisposition to autoimmunity..
36. Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu, Human mitochondrial transcriptional factor A breaks the mitochondria-mediated vicious cycle in Alzheimer’s disease, Sci Rep, 10.1038/srep37889, 6, 37889, 2016.11, [URL], In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA). Expression of hTFAM significantly improved cognitive function, reducing accumulation of both 8-oxoguanine, an oxidized form of guanine, in mtDNA and intracellular Aβ in 3xTg-AD mice and increasing expression of transthyretin, known to inhibit Aβ aggregation. Next, we found that AD model neurons derived from human induced pluripotent stem cells carrying a mutant PSEN1 (P117L) gene, exhibited mitochondrial dysfunction, accumulation of 8-oxoguanine and single-strand breaks in mtDNA, and impaired neuritogenesis with a decreased expression of transthyretin, which is known to be downregulated by oxidative stress. Extracellular treatment with recombinant hTFAM effectively suppressed these deleterious outcomes. Moreover, the treatment increased expression of transthyretin, accompanied by reduction of intracellular Aβ. These results provide new insights into potential novel therapeutic targets..
37. Kumiko Torisu, Xueli Zhang, Mari Nonak, Takahide Kaji, Daisuke Tsuchimoto, Kosuke Kajitani, SAKUMI Kunihiko, Torisu Takehiro, Kazuhiro Chida, Katsuo Sueishi, Michiaki Kubo, Jun Hata, Kitazono T, Yutaka Kiyohara, Yusaku Nakabeppu, PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice, Genes to Cells, 10.1111/gtc.12402, 21, 10, 1030-1048, 2016.10.
38. Yasuto Yoneshima, Nona Abolhassani, Teruaki Iyama, Kunihiko Sakumi, Naoko Shiomi, Masahiko Mori, Tadahiro Shiomi, Tetsuo Noda, Daisuke Tsuchimoto, Yusaku Nakabeppu, Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells, Sci Rep, 10.1038/srep32849, 6, 32849, 2016.09.
39. Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Morioka, Takashi Tachibana, Kohta Fujiwara, Noriko Yoshida, Shoji Notomi, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Yusaku Nakabeppu, Koh-Hei Sonoda, MUTYH promotes oxidative microglial activation and inherited retinal degeneration, JCI Insight, 10.1172/jci.insight.87781, 1, 15, e87781, 2016.09.
40. Mark D Evans, Vilas Mistry, Rajinder Singh, Daniel Gackowski, Rafal Rozalski, Agnieszka Siomek-Gorecka, David H Phillips, Jie Zuo, Leon Mullenders, Alex Pines, Yusaku Nakabeppu, Kunihiko Sakumi, Mutsuo Sekiguchi, Teruhisa Tsuzuki, Margherita Bignami, Ryszard Olinski, Marcus S Cooke, Nucleotide excision repair of oxidised genomic DNA is not a source of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, Free Radic Biol Med, 10.1016/j.freeradbiomed.2016.08.018, 99, 385-391, 2016.08.
41. Shizuka Takaku, Naoko Niimi, Toshihiko Kadoya, Hideji Yako, Masami Tsukamoto, Kunihiko Sakumi, Yusaku Nakabeppu, Hidenori Horie, Kazunori Sango, Galectin-1 and galectin-3 as key molecules for peripheral nerve degeneration and regeneration, AIMS Mol Sci, 10.3934/molsci.2016.3.325, 3, 3, 325-337, 2016.07.
42. Yuki Matsushita, Yasunari Sakai, Mitsunori Shimmura, Hiroshi Shigeto, Miki Nishio, Satoshi Akamine, Masafumi Sanefuji, Yoshito Ishizaki, Hiroyuki Torisu, Yusaku Nakabeppu, Akira Suzuki, Hidetoshi Takada, Toshiro Hara, Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice, Sci Rep, 10.1038/srep22991, 6, 22991, 2016.03.
43. Julio Leon, Kunihiko Sakumi, Erika Castillo, Zijing Sheng, Sugako Oka, Yusaku Nakabeppu, 8-Oxoguanine accumulation in mitochondrial DNA causes mitochondrial dysfunction and impairs neuritogenesis in cultured adult mouse cortical neurons under oxidative conditions., Sci Rep, 10.1038/srep22086, 6, 22086, 2016.02.
44. Bjorge, Monica D, Hildrestrand, Gunn A, Scheffler, Katja, Suganthan, Rajikala, Rolseth, Veslemoy, Kusnierczyk, Anna, Rowe, Alexander D, Vagbo, Cathrine B, Vetlesen, Susanne, Eide, Lars, Slupphaug, Geir, Nakabeppu, Yusaku, Bredy, Timothy W, Klungland, Arne, Bjoras, Magnar, Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice, Cell Reports, 10.1016/j.celrep.2015.12.001, 13, 12, 2671-2678, 2015.12.
45. Naoya Kubokura, Fumi Takahashi-Yanaga, Masaki Arioka, Tatsuya Yoshihara, Kazunobu Igawa, Katsuhiko Tomooka, Sachio Morimoto, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Takayuki Matsumoto, Takanari Kitazono, Toshiyuki Sasaguri, Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo, J Pharmacol Sci, 10.1016/j.jphs.2015.03.005, 127, 4, 446-455, 2015.04.
46. Yuko Kobayakawa, Kunihiko Sakumi, Kosuke Kajitani, Toshihiko Kadoya, Hidenori Horie, Jun-ichi Kira, Yusaku Nakabeppu, Galectin-1 deficiency improves axonal swelling of motor neurons in SOD1G93A transgenic mice, Neuropathol Appl Neurobiol, 10.1111/nan.12123, 41, 2, 227-244, 2015.02.
47. Sugako Oka, Julio Leon, Daisuke Tsuchimoto, Kunihiko Sakumi, Yusaku Nakabeppu, MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death, Oncogenesis, 10.1038/oncsis.2014.35, 3, e121, 2014.10, [URL].
48. Flandiana Yogianti, Makoto Kunisada, Eiji Nakano, Ryusuke Ono, Kunihiko Sakumi, Sugako Oka, Yusaku Nakabeppu, Chikako Nishigori, Inhibitory effects of dietary Spirulina platensis on UVB induced skin inflammatory responses and carcinogenesis, J Invest Dermatol, doi: 10.1038/jid.2014.188., 134, 10, 2610-2619, 2014.10.
49. Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, HIROYUKI HONDA, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu, Altered expression of diabetes-related genes in Alzheimer’s disease brains: The Hisayama study, Cereb Cortex, 10.1093/cercor/bht101, 24, 9, 2476-2488, 2014.09, Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM..
50. Hiroko Nomaru, Kunihiko Sakumi, Atsuhisa Katogi, Yoshinori N Ohnishi, Kosuke Kajitani, Daisuke Tsuchimoto, Eric J. Nestler, Yusaku Nakabeppu, Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia, Glia, 10.1002/glia.22680., 62, 8, 1284-1298, 2014.08.
51. Takuro Isoda, Yoshimichi Nakatsu, Jingshu Piao, Takashi Yao, Hiroshi Honda, Yusaku Nakabeppu, Teruhisa Tsuzuki, Abnormality in Wnt Signaling is Causatively Associated with Oxidative Stress-Induced Intestinal Tumorigenesis in MUTYH-Null Mice, Int. J. Biol. Sci., 10.7150/ijbs.9241, 10, 8, 940-947, 2014.08.
52. Jeroen E J Guikema, Erin K Linehan, Nada Esa, Daisuke Tsuchimoto, Yusaku Nakabeppu, Robert T. Woodland, Carol E. Schrader, Apurinic/Apyrimidinic Endonuclease 2 Regulates the Expansion of Germinal Centers by Protecting against Activation-Induced Cytidine Deaminase-Independent DNA Damage in B Cells, J Immunol, 10.4049/jimmunol.1400002, 193, 2, 931-939, 2014.07.
53. Fumi Takahashi, Tatsuya Yoshihara, Kentaro Jingushi, Kazuhiro Igawa, Katsuhiko Tomooka, Yutaka Watanabe, Sachio Morimoto, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Toshiyuki Sasaguri, DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3beta and expressions of cyclin D1 and TCF7L2 in cancer model mice, Biochem Pharmacol, 10.1016/j.bcp.2014.03.006., 89, 3, 340-348, 2014.06.
54. Janet Stavnezera, Erin K Linehan, Mikayla R. Thompsona, Robert T. Woodland, Ghaith Habboub, Anna J. Ucher, Tatenda Kadungure, Daisuke Tsuchimoto, Yusaku Nakabeppu, Carol E. Schrader, Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation, Proc Natl Acad Sci U S A, 10.1073/pnas.1405590111, 111, 25, 9217-9222, 2014.06.
55. Hideomi Hamasaki, Hiroyuki Honda, Satoshi O Suzuki, Masaaki Hokama, Yutaka Kiyohara, Yusaku Nakabeppu, Toru Iwaki, Down-regulation of MET in hippocampal neurons of Alzheimer's disease brains, Neuropathology, 10.1111/neup.12095, 34, 3, 284-290, 2014.06.
56. Mizuki Ohno, Kunihiko Sakumi, Ryutaro Fukumura, Masato Furuichi, Yuki Iwasaki, Masaaki Hokama, Toshimichi Ikemura, Teruhisa Tsuzuki, Yoichi Gondo, Yusaku Nakabeppu, 8-oxoguanine causes spontaneous de novo germline mutations in mice, Sci Rep, 10.1038/srep04689, 4, 4689, 2014.04.
57. Jalland, C. M., Benestad, S. L., Ersdal, C., Scheffler, K., Suganthan, R., Nakabeppu, Y., Eide, L., Bjoras, M., Tranulis, M. A., Accelerated clinical course of prion disease in mice compromised in repair of oxidative DNA damage, Free Radic Biol Med, 10.1016/j.freeradbiomed.2013.11.013., 68, 1-7, 2014.03.
58. Kajitani, K., Kobayakawa Y., Nomaru, H., Kadoya, T., Horie, H., Nakabeppu, Y., Characterization of galectin-1-positive cells in the mouse hippocampus, NeuroReport, 10.1097/WNR.0000000000000068, 25, 3, 171-176, 2014.02.
59. Murakami, N., Ohtsubo, T., Kansui, Y., Goto, K., Noguchi, H., Haga, Y., Nakabeppu, Y., Matsumura, K., Kitazono, T., Mice Heterozygous for the Xanthine Oxidoreductase Gene Facilitate Lipid Accumulation in Adipocytes, Arterioscler Thromb Vasc Biol, 10.1161/ATVBAHA.113.302214, 34, 1, 44-51, 2014.01.
60. Matsumoto, A., Yamafuji M., Tachibana, T., Nakabeppu, Y., Noda. M., Nakaya, H., Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice, Sci Rep, 10.1038/srep03273, 3, 3273, 2013.11.
61. Yasunari Sakai, Kazuhiro Ohkubo, Yuki Matsushita, Satoshi Akamine, Ishizaki Yoshito, Hiroyuki Torisu, Kenji Ihara, Masafumi Sanefuji, Min-Seon Kim, Ki-Up Lee, Chad A Shaw, Janghoo Lim, Yusaku Nakabeppu, Toshiro Hara, Neuroendocrine phenotypes in a boy with 5q14 deletion syndrome implicate the regulatory roles of myocyte-specific enhancer factor 2C in the postnatal hypothalamus., Eur J Med Genet, doi: 10.1016/j.ejmg.2013.06.009, 56, 9, 475-483, 2013.09.
62. Hideo Tsuji, Hiroko Ishii-Ohba, Tadahiro Shiomi, Naoko Shiomi, Takanori Katsube, Masahiko Mori, Mitsuru Nenoi, Ohno Mizuki, Daisuke Yoshimura, Sugako OKa, Yusaku Nakabeppu, Kouichi Tasumi, Masahiro Muto, Toshikiko Sada, Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice, J Radiat Res, 10.1093/jrr/rrs128, 54, 3, 453-466, PMID: 23297316, 2013.05.
63. Noriko Yutsudo, Takkashi Kamada, Kosuke Kajitani, Hiroko Nomaru, Atsuhisa Katogi, Yoko H Ohnishi, Yoshinori N Ohnisi, Kei-ichiro Takase, Hiroshu Shugeto, SAKUMI Kunihiko, Yusaku Nakabeppu, fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior, Neuropsychopharmacology, doi:10.1038/npp.2012.260, 38, 5, 895-906, 2013.04.
64. Yukari Koga, Miyuki Inazato, Teruya Nakamura, Chie Hashikawa, Mami Chirifu, Asuka Michi, Taku Yamashita, Sachiko Toma, Akihiko Kuniyasu, Shinji Ikemizu, Yusaku Nakabeppu, Yuriko Yamagataa, Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus, Acta Crystallogr Sect F Struct Biol Cryst Commun, 10.1107/S1744309112048002, 69, Pt1, 45-48, 2013.01.
65. Shizuka Takaku, Hiroko Yanagisawa, Kazuhiko Watabe, Hidenori Horie, Toshihiko Kadoya, Kunihiko Sakumi, Yusaku Nakabeppu, Françoise Poirier, Kazunori Sango, GDNF promotes neurite outgrowth and upregulates galectin-1 through the RET/PI3K signaling in cultured adult rat dorsal root ganglion neurons, Neurochemistry International, 10.1016/j.neuint.2013.01.008, 62, 3, 330-339, 2013.01.
66. Harini Sampath, Vladimir Vartanian, M. Rick Rollins, Kunihiko Sakumi, Yusaku Nakabeppu, R. Stephen Lloyd, 8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction, PLoS ONE, 10.1371/journal.pone.0051697, 7, 12, e51697, 2012.12.
67. Zijing Sheng, Sugako Oka, Daisuke Tsuchimoto, Abolhassani Nona, Nomaru Hiroko, Kunihiko Sakumi, Yamada Hidetaka, Yusaku Nakabeppu, 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair, J Clin Invest, 10.1172/JCI65053, 122, 12, 4344-4361, 2012.12.
68. Yogianti F, Kunisada M, Ono R, Sakumi K, Nakabeppu Y, Nishigori C., Skin tumours induced by narrowband UVB have higher frequency of p53 mutations than tumours induced by broadband UVB independent of Ogg1 genotype, Mutagenesis, doi: 10.1093/mutage/ges029., 27, 6, 637-643, 2012.11.
69. Murakami Y, Ikeda Y, Yoshida N, Notomi S, Hisatomi T, Oka S, De Luca G, Yonemitsu Y, Bignami M, Nakabeppu Y, Ishibashi T., MutT Homolog-1 Attenuates Oxidative DNA Damage and Delays Photoreceptor Cell Death in Inherited Retinal Degeneration, Am J Pathol, doi: 10.1016/j.ajpath.2012.06.026, 181, 4, 1378-1386, 2012.10.
70. Nishimura Y, Takiguchi S, Yoshioka K, Nakabeppu Y, Itoh K., Silencing of SNX1 by siRNA stimulates the ligand-induced endocytosis of EGFR and increases EGFR phosphorylation in gefitinib-resistant human lung cancer cell lines, Int J Oncol, doi: 10.3892/ijo.2012.1578, 2012.06.
71. Kunisada M, Yogianti F, Sakumi K, Ono R, Nakabeppu Y, Nishigori C , Increased Expression of Versican in the Inflammatory Response to UVB- and Reactive Oxygen Species-Induced Skin Tumorigenesis, Am J Pathol, 179, 6, 3056-3065, 2011.12.
72. Ohnishi YN, Ohnishi YH, Hokama M, Nomaru H, Yamazaki K, Tominaga Y, Sakumi K, Nestler EJ, Nakabeppu Y, FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔFosB, Biological Psychiatry, 186, 4, 1943-1950, 2011.09.
73. Iwama E, Tsuchimoto D, Iyama T, Sakumi K, Nakagawara A, Takayama K, Nakanishi Y, Nakabeppu Y., Cancer-Related PRUNE2 Protein Is Associated with Nucleotides and Is Highly Expressed in Mature Nerve Tissues, J Mol Neurosci, 10.1007/s12031-010-9490-2, 44, 2, 103-114, 2011.06.
74. Nishimura Y, Yoshioka K, Takiguchi S, Bereczky B, Nakabeppu Y, Itoh K, A Role for SNX1 in the Regulation of EGF-Dependent Phosphorylated EGFR Endocytosis Via the Early/Late Endocytic Pathway in a Gefitinib- Sensitive Human Lung Cancer Cells, Current Signal Transduction Therapy, 6, 3, 383-395, 2011.06.
75. Guikema JE, Gerstein RM, Linehan EK, Evan-Browning E, Tsuchimoto D, Nakabeppu Y, Schrader CE, Apurinic/Apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge, J Immunol, 186, 4, 1943-1950, 2011.02.
76. Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H., Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer, Hum Mutat, 31, 11, E1861-1874., 2010.11.
77. Iyama T, Abolhassani N, Tsuchimoto D, Nonaka M, Nakabeppu Y., NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest, Nucleic Acids Research, 38, 14, 4834-4843, 2010.06.
78. Abolhassani, N, Iyama, T, Tsuchimoto, D, Sakumi, K, Ohno, M, Behmanesh, M, Nakabeppu, Y., NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals, Nucleic Acids Research, 38, 9, 2891-2903, 2010.05.
79. Martin SA, McCabe N, Mullarkey M, Cummins R, Burgess DJ, Nakabeppu Y, Oka S, Kay E, Lord CJ, Ashworth A. , DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1, Cancer Cell, 17, 3, 1235-1248, 2010.03.
80. Behmanesh, M., Sakumi, K., Abolhassani, N., Toyokuni, S., Oka, S., Ohnishi, Y., Tsuchimoto, D., and Nakabeppu, Y. , ITPase-deficient mice show growth retardation and die before weaning, Cell Death Differ, 16, 10, 1315-1322, 2009.10.
81. Gushima M, Hirahashi M, Matsumoto T, Fujita K, Fujisawa R, Mizumoto K, Nakabeppu Y, Iida M, Yao T, Tsuneyoshi M., Altered expression of MUTYH and an increase in 8-hydroxydeoxyguanosine are early events in ulcerative colitis-associated carcinogenesis, J Pathol, 219, 1, 77-86, 2009.09.
82. Kyota Fujita, Toshihiro Seike, Noriko Yutsudo, Mizuki Ohno, Hidetaka Yamada, Hiroo Yamaguchi, Kunihiko Sakumi, Yukiko Yamakawa, Mizuho A. Kido, Atsushi Takaki, Toshihiko Katafuchi, Yoshinori Tanaka, Yusaku Nakabeppu, Mami Noda , Hydrogen in Drinking Water Reduces Dopaminergic Neuronal Loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Parkinson’s Disease, PLoS ONE, 4, 9, e7247, 2009.09.
83. Sabouri Z, Okazaki IM, Shinkura R, Begum N, Nagaoka H, Tsuchimoto D, Nakabeppu Y, Honjo T., Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes, Int Immunol, 21, 8, 947-955, 2009.08.
84. Kajitani, K., Nomaru, H., Ifuku, M., Yutsudo, N., Dan, Y., Miura, T., Tsuchimoto, D., Sakumi, K., Kadoya, T., Horie, H., Poirier, F., Noda, M. and Nakabeppu, Y., Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus, Cell Death Differ, 16, 3, 417-427, 2009.03.
85. Nonaka, M., Tsuchimoto, D., Sakumi, K. and Nakabeppu, Y., Mouse RS21-C6 is a mammalian 2’-deoxycytidine 5’-triphosphate pyrophosphohydrolase, preferring 5-iodocytosine, FEBS J, 276, 6, 1654-1666, 2009.03.
86. Nakane, H., Hirota, S., Brooks, P. J., Nakabeppu, Y., Nakatsu, Y., Nishimune, Y., Iino, A., and Tanaka, K. , Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice. , DNA Repair, 7, 12, 1938-1950, 2008.12.
87. Ohnishi YN, Sakumi K, Yamazaki K, Ohnishi YH, Miura T, Tominaga Y, Nakabeppu Y., Antagonistic regulation of cell-matrix adhesion by FosB and ΔFosB/Δ2ΔFosB encoded by alternatively spliced forms of fosB transcripts., Mol Biol Cell, 19(11): 4717-4729, 2008.11.
88. De Luca, G., Russo, M.T., Degan, P., Tiveron, C., Zijno, A., Meccia, E., Ventura, I., Mattei, E., Nakabeppu, Y., Crescenzi, M., Pèpponi, R., Pzzola, A., Popoli, P. and Bignami, M., A Role for Oxidized DNA Precursors in Huntington's Disease-Like Striatal Neurodegeneration, PLoS Genet, 4, 11, e1000266, 2008.11.
89. Dan Y, Ohta Y, Tsuchimoto D, Ohno M, Ide Y, Sami M, Kanda T, Sakumi K, Nakabeppu Y., Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null thymus., DNA Repair, 7 (9): 1437-1454, 2008.09.
90. Yamamoto, S., Tanaka, K., Sakimura, R., Okada, T., Nakamura, T., Li, Y., Takasaki, M., Nakabeppu, Y., and Iwamoto, Y. , Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in Chondrosarcoma cell lines, Anticancer Research, 28: 1585-1592, 2008.07.
91. Yanaru-Fujisawa R, Matsumoto T, Ushijima Y, Esaki M, Hirahashi M, Gushima M, Yao T, Nakabeppu Y, Iida M., Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis., Clin Genet, 73(6):545-553, 2008.06.
92. Ichikawa J, Tsuchimoto D, Oka S, Ohno M, Furuichi M, Sakumi K, Nakabeppu Y., Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death., DNA Repair, 7(3):418-430, 2008.03.
93. Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y., Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs., EMBO Journal., 27(2):421-432., 2008.01.
94. Kunisada M, Kumimoto H, Ishizaki K, Sakumi K, Nakabeppu Y, Nishigori C., Narrow-band UVB induces more carcinogenic skin tumors than broad-band UVB through the formation of cyclobutane pyrimidine dimer., The Journal of Investigative Dermatology, 127(12):2865-2871., 2007.12.
95. Guikema JE, Linehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR, Stavnezer J, Schrader CE., APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination., Journal of Experimental Medicine, 204(12):3017-3026, 2007.11.
96. Sakamoto K, Tominaga Y, Yamauchi K, Nakatsu Y, Sakumi K, Yoshiyama K, Egashira A, Kura S, Yao T, Tsuneyoshi M, Maki H, Nakabeppu Y, Tsuzuki T., MUTYH-null mice are susceptible to spontaneous and oxidative stress induced intestinal tumorigenesis., Cancer Research, 67(14):6599-6604. , 2007.07.
97. Kuraoka I, Suzuki K, Ito S, Hayashida M, Kwei JS, Ikegami T, Handa H, Nakabeppu Y, Tanaka K., RNA polymerase II bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS., DNA Repair, 6, 6, 841-851, 2007.06.
98. Ohtsubo T, Ohya Y, Nakamura Y, Kansui Y, Furuichi M, Matsumura K, Fujii K, Iida M, Nakabeppu Y., Accumulation of 8-oxo-deoxyguanosine in cardiovascular tissues with the development of hypertension., DNA Repair, 6, 6, 760-769, 2007.06.
99. Miyata K, Yasukawa T, Fukuda M, Takeuchi T, Yamazaki K, Sakumi K, Tamamori-Adachi M, Ohnishi Y, Ohtsuki Y, Nakabeppu Y, Kitajima S, Onishi S, Aso T., Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A., Cell Death Differ, 14(4):716-726, 2007.04.
100. Nakamura T, Kitaguchi Y, Miyazawa M, Kamiya H, Toma S, Ikemizu S, Shirakawa M, Nakabeppu Y, Yamagata Y., Crystallization and preliminary X-ray analysis of human MTH1 complexed with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP., Acta Crystallograph Sect F Struct Biol Cryst Commun., 62(Pt 12):1283-1285, 2006.12.
101. Kamiya H, Cadena-Amaro C, Dugue L, Yakushiji H, Minakawa N, Matsuda A, Pochet S, Nakabeppu Y, Harashima H., Recognition of Nucleotide Analogs Containing the 7,8-Dihydro-8-oxo Structure by the Human MTH1 Protein., J. Biochem., 140(6):843-849, 2006.12.
102. Arima T, Yamasaki K, John RM, Kato K, Sakumi K, Nakabeppu Y, Wake N, Kono T., The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice., Genomics., 88(5):650-658, 2006.11.
103. Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, Verhofstad N, Nakabeppu Y, Baum LG, Bakkers J, Mayo KH, Poirier F, Griffioen AW., Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy., Proc Natl Acad Sci U S A., 103(43):15975-15980, 2006.10.
104. Akatsuka S, Aung TT, Dutta KK, Jiang L, Lee WH, Liu YT, Onuki J, Shirase T, Yamasaki K, Ochi H, Naito Y, Yoshikawa T, Kasai H, Tominaga Y, Sakumi K, Nakabeppu Y, Kawai Y, Uchida K, Yamasaki A, Tsuruyama T, Yamada Y, Toyokuni S., Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis., Am. J. Pathol., 169(4):1328-1342, 2006.10.
105. Arai T, Fukae J, Hatano T, Kubo S, Ohtsubo T, Nakabeppu Y, Mori H, Mizuno Y, Hattori N., Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease., Acta Neuropathol, 112(2):139-145., 2006.08.
106. Sakai Y, Oda H, Yoshimura D, Furuichi M, Kang D, Iwai S, Hara T, Nakabeppu Y., The GT to GC single nucleotide polymorphism at the beginning of an alternative exon 2C of human MTH1 gene confers an amino terminal extension that functions as a mitochondrial targeting signal., J. Mol. Med., 4(8):660-670, 2006.08.
107. Arima, H., Kiyohara Y., Tanizaki Y., Nakabeppu Y., Kubo M., Kato I., Sueishi K., Tsuneyoshi M., Fujishima M. and Iida M, Angiotensin I-converting enzyme gene polymorphism modifies the smoking-cancer association: the Hisayama Study., Europ. J. Cancer Prev., 5(3):196-201, 2006.06.
108. Ohno M, Miura T, Furuichi M, Tominaga Y, Tsuchimoto D, Sakumi K, Nakabeppu Y., A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome., Genome Res., 6(5):567-575, 2006.05.
109. Powell, K. J., Binder T. L., Hori S., Nakabeppu Y., R. D., Weinberger, Lipska B. K. and Robertson G. S., Neonatal Ventral Hippocampal Lesions Produce an Elevation ofΔFosB-like Protein(s) In the Rodent Neocortex., Neuropsychopharmacol., 31(4):700-711, 2006.04.
110. Yamaguchi, H., Kajitani K., Dan Y., Furuichi M., Ohno M., Sakumi K., Kang D. and Nakabeppu Y., MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine., Cell Death Differ, 13(4):551-563, 2006.04.
111. Nakamura TY, Jeromin A, Smith G, Kurushima H, Koga H, Nakabeppu Y, Wakabayashi S, Nabekura J., Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons., J. Cell Biol., 172(7):1081-1091, 2006.03.
112. Kajitani, K., Yamaguchi H., Dan Y., Furuichi M., Kang D. and Nakabeppu Y., MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity., J. Neurosci., 26(6):1688-1698, 2006.02.
113. Torisu, K., Tsuchimoto D., Ohnishi Y. and Nakabeppu Y., Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein., J. Biochem., 10.1093/jb/mvi168, 138, 6, 763-772, 138(6):763-772, 2005.12.
114. Sato, T., Hidaka K., Iwanaga A., Ito M., Asano M., Nakabeppu Y., Morisaki T. and Yoshioka K., Impairment of cardiomyogenesis in embryonic stem cells lacking scaffold protein JSAP1., Biochem. Biophys. Res. Commun., 10.1016/j.bbrc.2005.10.052, 338, 2, 1152-1157, 338 (2):1152-1157., 2005.12.
115. Wei, P., Taniguchi S., Sakai Y., Imamura M., Inoguchi T., Nawata H., Oda S., Nakabeppu Y., Nishimura J. and Ikuyama S., Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages., J. Biochem., 10.1093/jb/mvi136, 138, 4, 399-412, 138 (4):399-412., 2005.10.
116. Kurushima, H., Ohno M., Miura T., Nakamura T. Y., Horie H., Kadoya T., Ooboshi H., Kitazono T., Ibayashi S., Iida M. and Nakabeppu Y., Selective induction of ΔFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of ΔFosB and galectin-1 in neuroprotection and neurogenesis., Cell Death Differ, 10.1038/sj.cdd.4401648, 12, 8, 1078-1096, 12 (8):1078-1096., 2005.08.
117. Kunisada, M., Sakumi K., Tominaga Y., Budiyanto A., Ueda M., Ichihashi M., Nakabeppu Y. and Nishigori C., 8-Oxoguanine Formation Induced by Chronic UVB Exposure Makes Ogg1 Knockout Mice Susceptible to Skin Carcinogenesis., Cancer Res, 10.1158/0008-5472.CAN-05-0724, 65, 14, 6006-6010, 65 (14):6006-10., 2005.07.
118. Campalans, A., Marsin S., Nakabeppu Y., O'Connor T R., Boiteux S. and Radicella J. P., XRCC1 interactions with multiple DNA glycosylases: A model for its recruitment to base excision repair., DNA Repair, 10.1016/j.dnarep.2005.04.014, 4, 7, 826-835, 4 (7):826-35., 2005.07.
119. Tamura, K., Hua B., Adachi S., Guney I., Kawauchi J., Morioka M., Tamamori-Adachi M., Tanaka Y., Nakabeppu Y., Sunamori M., Sedivy J. M. and Kitajima S., Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation., EMBO J, 10.1038/sj.emboj.7600742, 24, 14, 2590-2601, 24 2590-2601, 2005.06.
120. Fukae, J., Takanashi M., Kubo S.-i., Nishioka K.-i., Nakabeppu Y., Mori H., Mizuno Y. and Hattori N., Expression of 8-oxoguanine DNA glycosylase (OGG1) in Parkinson's disease and related neurodegenerative disorders., Acta Neurophathologica, 10.1007/s00401-004-0937-9, 109, 3, 256-262, 109 (3):256-262., 2005.03.
121. Behmanesh, M., Sakumi K., Tsuchimoto D., Torisu K., Ohnishi-Honda Y., Derrick E R. and Nakabeppu Y., Characterization of the structure and expression of mouse Itpa gene and its related sequences in the mouse genome., DNA Research, 10.1093/dnares/12.1.39, 12, 1, 39-51, 12 (1):29-41., 2005.02.
122. Furuya, H., Shinnoh N., Ohyagi Y., Ikezoe K., Kikuchi H., Osoegawa M., Fukumaki Y., Nakabeppu Y., Hayashi T., Kira J.-i. and Abe M., Some flavonoids and DHEA-S prevent the cis-effect of expanded CTG repeats in a stable PC12 cell transformant., Biochemical Pharmacology, 10.1016/j.bcp.2004.10.005, 69, 3, 503-516, 69 (3):503-516., 2005.02.
123. Ushijima, Y., Y. Tominaga, T. Miura, Daisuke Tsuchimoto, K. Sakumi, and Y. Nakabeppu., A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA., Nucleic Acids Res., 10.1093/nar/gki214, 33, 2, 672-682, 33(2):672-682., 2005.01.
124. Robertson, G. S., C. J. Lee, K. Sridhar, Y. Nakabeppu, M. Cheng, Y.-M. Wang, and M. G. Caron., Clozapine-, but not haloperidol-, induced increases in deltaFosB-like immunoreactivity is completely blocked in the striatum of mice lacking D3 dopamine receptors, Eur. J. Neurosci., 10.1111/j.1460-9568.2004.03774.x, 20, 11, 3189-3194, 20(11):3189-3194., 2004.12.
125. Ide, Y., Tsuchimoto, D., Tominaga, Y., Nakashima, M., Watanabe, T., Sakumi, K., Ohno, M. and Nakabeppu, Y., Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice., Blood, 10.1182/blood-2004-04-1476, 104, 13, 4097-4103, 104(13):4097-4103, 2004.12.
126. Keiji Hashimoto, Yusaku Nakabeppu, Masaaki Moriya, Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair, Nucleic Acids Res., 10.1093/nar/gkh909, 32, 19, 5928-5934, 32(19):5928-5234, 2004.11.
127. Nunoshiba, T., R. Ishida, S. Sasaki, S. Iwai, Nakabeppu, Y. and Yamamoto, K., A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c ( PCD1 gene) in Saccharomyces cerevisiae, Nucelic Acids Res., 10.1093/nar/gkh868, 32, 18, 5339-5348, 32(18):5339-5348, 2004.10.
128. T. Miura, M. Takahashi, H. Horie, H. Kurushima, D. Tsuchimoto, K. Sakumi, Y. Nakabeppu, Galectin-1beta, a natural monomeric form of galectin-1 lacking its six amino-terminal residues promotes axonal regeneration but not cell death., Cell Death and Differentiation, 10.1038/sj.cdd.4401462, 11, 10, 1076-1083, 11(10):1076-1083, 2004.10.
129. Masaki Mishima, Yasunari Sakai, Noriyuki Itoh, Hiroyuki Kamiya, Masato Furuichi, Masayuki Takahashi, Yuriko Yamagata, Shigenori Iwai, Yusaku Nakabeppu, Masahiro Shirakawa, Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates., J. Biol. Chem., 10.1074/jbc.M402393200, 279, 32, 33806-33815, 279(32):33806-33815, 2004.08.
130. Yohei Tominaga, Yasuhiro Ushijima, Daisuke Tsuchimoto, Masaki Mishima, Masahiro Shirakawa, Seiki Hirano, Kunihiko Sakumi, Yusaku Nakabeppu., MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain., Nucleic Acids Res., 10.1093/nar/gkh642, 32, 10, 3198-3211, 32 (10):3198-3211, 2004.06.
131. Kimura, Y., S. Oda, A. Egashira, Y. Kakeji, H. Baba, Y. Nakabeppu, and Y. Maehara., A variant form of hMTH1, a human homologue of mutT E. coli mutator gene, correlates with somatic mutation in p53 tumour suppressor gene in gastric cancer patients., J. Med. Genet., 10.1136/jmg.2003.013268, 41, 5, 41 (5): e57, 2004.05.
132. Iida, T., Furuta, A., Nakabeppu, Y., and Iwaki, T., Defense mechanism to oxidative DNA damage in glial cells., Neuropathol., 10.1111/j.1440-1789.2003.00540.x, 24, 2, 125-130, 24 (2): 125-130, 2004.05.
133. Kamiya, H., H. Yakushiji, L. Dugue, M. Tanimoto, S. Pochet, Y. Nakabeppu, H. Harashima., Probing the substrate recognition mechanism of the human MTH1 protein by nucleotide analogs., J. Mol. Biol., 10.1016/j.jmb.2003.12.060, 336, 4, 843-850, 336 (4): 843-850, 2004.02.
134. Ichinoe, A., M. Behmanesh, Y. Tominaga, Y. Ushijima, S. Hirano, Y. Sakai, D. Tsuchimoto, K. Sakumi, N. Wake, Y. Nakabeppu., Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts., Nucleic Acids Res., 10.1093/nar/gkh214, 32, 2, 477-487, 32(2):477-487, 2004.01.
135. Russo, M. T., M. F. Blasi, F. Chiera, P. Fortini, P. Degan, P. Macpherson, M. Furuichi, Y. Nakabeppu, P. Karran, G. Aquilina, and M. Bignami., The oxidized Deoxynucleotide Triphosphate Pool is a Significant Contributor to Genetic Instability in Mismatch Repair-Deficient Cells., Mol. Cell Biol., 10.1128/MCB.24.1.465-474.2004, 24, 1, 465-474, 24: 465-474., 2004.01.
136. Nakagawachi, T., H. Soejima, Z. Wei, T. Urano, S. Matsukura, K. Higashimoto, Y. Satoh, Y. Kitajima, H. Harada, K. Furukawa, H. Matsuzaki, M. Emi, K. Miyazaki, Y. Nakabeppu, M. Sekiguchi, and T. Mukai., Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer., Oncogene, 10.1038/sj.onc.1207183, 22, 55, 8835-8844, 22:8835-8844, 2003.12.
137. Xu, P., K. Yoshioka, D. Yoshimura, Y. Tominaga, T. Nishioka, M. Ito, and Y. Nakabeppu., In vitro development of mouse embryonic stem cells lacking JSAP1 scaffold protein revealed its requirement during early embryonic neurogenesis., J. Biol. Chem., 10.1074/jbc.M307888200, 278, 48, 48422-48433, 278:48422-48433, 2003.11.
138. Hirano, S., Y. Tominaga, A. Ichinoe, Y. Ushijima, D. Tsuchimoto, Y. Honda-Ohnishi, T. Ohtsubo, K. Sakumi, and Y. Nakabeppu., Mutator phenotype of MUTYH-null mouse embryonic stem cells., J. Biol. Chem., 10.1074/jbc.C300316200, 278, 40, 38121-38124, 278:38121-38124, 2003.10.
139. Yoshimura, D., K. Sakumi, M. Ohno, Y. Sakai, M. Furuichi, S. Iwai, and Y. Nakabeppu., An oxidized purine nucleoside triphosphatase, MTH1 suppresses cell death caused by oxidative stress., J. Biol. Chem., 278:37965-37973, 2003.09.
140. Yuan, Q., K. Matsumoto, Y. Nakabeppu, and T. Iwaki., A comparative immunohistochemistry of O6-methylguanine-DNA methyltransferase and p53 in diffusely infiltrating astrocytomas., Neuropathol., 10.1046/j.1440-1789.2003.00504.x, 23, 3, 203-209, 23:203-209, 2003.09.
141. Tahara, K., D. Tsuchimoto, Y. Tominaga, S. Asoh, S. Ohta, M. Kitagawa, H. Horie, T. Kadoya, and Y. Nakabeppu., ΔFosB but not FosB Induces Delayed Apoptosis Independent of Cell Proliferation in the Rat1a Embryo Cell Line., Cell Death Diff., 10.1038/sj.cdd.4401173, 10, 5, 496-507, 10:496-507, 2003.04.
142. Yamazaki, K., T. Aso, Y. Ohnishi, M. Ohno, K. Tamura, T. Shuin, S. Kitajima, and Y. Nakabeppu., Mammalian elongin A is not essential for cell viability but required for proper cell-cycle progression with limited alteration of gene expression., J. Biol. Chem., 10.1074/jbc.C300047200, 278, 15, 13585-13589, 278:13585-13589, 2003.04.
143. Sakumi, K., Y. Tominaga, M. Furuichi, P. Xu, T. Tsuzuki, M. Sekiguchi, and Y. Nakabeppu., Ogg1 Knockout-associated Lung Tumorigenesis and Its Suppression by Mth1 Gene Disruption., Cancer Res., 63, 5, 902-905, 63:902-905, 2003.03.
144. Matsukura, S., H. Soejima, T. Nakagawachi, H. Yakushiji, A. Ogawa, M. Fukuhara, K. Miyazaki, Y. Nakabeppu, M. Sekiguchi, and T. Mukai., CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection., Br. J. Cancer, 10.1038/sj.bjc.6600743, 88, 4, 521-529, 88:521-529, 2003.02.
145. Tsuruya, K., M. Furuichi, Y. Tominaga, M. Shinozaki, M. Tokumoto, T. Yoshimitsu, K. Fukuda, H. Kanai, H. Hirakata, M. Iida, and Y. Nakabeppu., Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney., DNA Repair, 10.1016/S1568-7864(02)00214-8, 2, 2, 211-229, 2:211-229, 2003.02.
146. Ide, Y., D. Tsuchimoto, Y. Tominaga, Y. Iwamoto, and Y. Nakabeppu., Characterization of the genomic structure and expression of the mouse Apex2 gene., Genomics, 10.1016/S0888-7543(02)00009-5, 81, 1, 47-57, 81:47-57, 2003.01.
147. Arima, H., Y. Kiyohara, Y. Tanizaki, Y. Nakabeppu, M. Kubo, I. Kato, K. Sueishi, M. Tsuneyoshi, M. Fujishima, and M. Iida., Detection of angiotensin-converting enzyme gene insertion/deletion polymorphism from paraffin-embedded tissues: the Hisayama study., Circ. J., 10.1253/circj.66.1034, 66, 11, 1034-1036, 66:1034-1036, 2002.11.
148. Zhang, D., L. Zhang, D. W. Lou, Y. Nakabeppu, J. Zhang, and M. Xu, The dopamine D1 receptor is a critical mediator for cocaine-induced gene expression., J. Neurochem., 10.1046/j.1471-4159.2002.01089.x, 82, 6, 1453-1464, 82:1453-1464, 2002.09.
149. Yamazaki, K., L. Guo, K. Sugahara, C. Zhang, H. Enzan, Y. Nakabeppu, S. Kitajima, and T. Aso., Identification and biochemical characterization of a novel transcription elongation factor elongin A3., J. Biol. Chem., 10.1074/jbc.M202859200, 277, 29, 26444-26451, 277:26444-26451, 2002.06.
150. Nunoshiba, T., T. Watanabe, Y. Nakabeppu, and K. Yamamotoa., Mutagenic target for hydroxyl radicals generated in Escherichia coli mutant deficient in Mn- and Fe-superoxide dismutases and Fur, a repressor for iron-uptake systems., DNA Repair, 10.1016/S1568-7864(02)00014-9, 1, 5, 411-418, 1:411-418, 2002.05.
151. Takahashi, M., F. Maraboeuf, Y. Sakai, H. Yakushiji, M. Mishima, M. Shirakawa, S. Iwai, H. Hayakawa, M. Sekiguchi, and Y. Nakabeppu., Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein., J. Mol. Biol., 10.1016/S0022-2836(02)00163-8, 319, 1, 129-139, 319:129-139, 2002.05.
152. Kohya, N., K. Miyazaki, S. Matsukura, H. Yakushiji, Y. Kitajima, K. Kitahara, M. Fukuhara, Y. Nakabeppu, and M. Sekiguchi., Deficient Expression of O(6)-Methylguanine-DNA Methyltransferase Combined With Mismatch-Repair Proteins hMLH1 and hMSH2 Is Related to Poor Prognosis in Human Biliary Tract Carcinoma., Ann. Surg. Oncol., 10.1245/aso.2002.9.4.371, 9, 4, 371-379, 9:371-379, 2002.05.
153. Nishioka, T., K. Sakumi, T. Miura, K. Tahara, H. Horie, T. Kadoya, and Y. Nakabeppu., fosB gene products trigger cell proliferation and morphological alteration with an increased expression of a novel processed form of galectin-1 in the rat 3Y1 embryo cell line., J. Biochem., 131, 5, 653-661, 131:653-661, 2002.05.
154. Kikuchi, H., A. Furuta, K. Nishioka, S. O. Suzuki, Y. Nakabeppu, and T. Iwaki., Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis., Acta Neuropathol., 10.1007/s00404-001-0480-x, 103, 4, 408-414, 103:408-414, 2002.04.
155. Kato, K., S. Horiuchi, A. Takahashi, Y. Ueoka, T. Arima, T. Matsuda, H. Kato, J. Nishida Ji, Y. Nakabeppu, and N. Wake., Contribution of Estrogen Receptor alpha to Oncogenic K-Ras-mediated NIH3T3 Cell Transformation and Its Implication for Escape from Senescence by Modulating the p53 Pathway., J. Biol. Chem., 10.1074/jbc.M107391200, 277, 13, 11217-11224, 277:11217-11224, 2002.03.
156. Sakai, Y., M. Furuichi, M. Takahashi, M. Mishima, S. Iwai, M. Shirakawa, and Y. Nakabeppu., A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-Oxo-dGTP by human MTH1., J. Biol. Chem., 10.1074/jbc.M110566200, 277, 10, 8579-8587, 277:8579-8587, 2002.03.
157. Hayashi, H., Y. Tominaga, S. Hirano, A. E. McKenna, Y. Nakabeppu, and Y. Matsumoto., Replication-Associated Repair of Adenine:8-Oxoguanine Mispairs by MYH., Current Biol., 10.1016/S0960-9822(02)00686-3, 12, 4, 335-339, 12:335-339, 2002.02.
158. Fujikawa, K., H. Yakushiji, Y. Nakabeppu, T. Suzuki, M. Masuda, H. Ohshima, and H. Kasai., 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog., FEBS Lett., 10.1016/S0014-5793(02)02240-8, 512, 1-3, 149-151, 512:149-151, 2002.02.
159. Iida, T., A. Furuta, K. Nishioka, Y. Nakabeppu, and T. Iwaki., Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain., Acta Neuropathol., 103, 1, 20-25, 103:20-25, 2002.01.
160. Matsukura, S., K. Miyazaki, H. Yakushiji, A. Ogawa, K. Harimaya, Y. Nakabeppu, and M. Sekiguchi., Expression and prognostic significance of O6-methylguanine-DNA methyltransferase in hepatocellular, gastric, and breast cancers., Ann. Surg. Oncol., 10.1245/aso.2001.8.10.807, 8, 10, 807-816, 8:807-816, 2001.12.
161. Tsuzuki, T., A. Egashira, H. Igarashi, T. Iwakuma, Y. Nakatsuru, Y. Tominaga, H. Kawate, K. Nakao, K. Nakamura, F. Ide, S. Kura, Y. Nakabeppu, M. Katsuki, T. Ishikawa, and M. Sekiguchi., Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase., Proc. Natl. Acad. Sci. U. S. A., 10.1073/pnas.191086798, 98, 20, 11456-11461, 98:11456-11461, 2001.09.
162. Furuta, A., T. Iida, Y. Nakabeppu, and T. Iwaki., Expression of hMTH1 in the hippocampi of control and Alzheimer's disease., Neuroreport, 10.1097/00001756-200109170-00028, 12, 13, 2895-2899, 12:2895-2899, 2001.09.
163. Jaiswal, M., N. F. LaRusso, K. Nishioka, Y. Nakabeppu, and G. J. Gores., Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide., Cancer Res., 61, 17, 6388-6393, 61:6388-6393, 2001.09.
164. Kasprzak, K. S., Y. Nakabeppu, T. Kakuma, Y. Sakai, K. Tsuruya, M. Sekiguchi, J. M. Ward, B. A. Diwan, K. Nagashima, and B. H. Kasprzak., Intracellular Distribution of the Antimutagenic Enzyme MTH1 in the Liver, Kidney, and Testis of F344 Rats and its Modulation by Cadmium., Exp. Toxico. Pathol., 10.1078/0940-2993-00201, 53, 5, 325-335, 53:325-336, 2001.07.
165. Tsuchimoto, D., Y. Sakai, K. Sakumi, K. Nishioka, M. Sasaki, T. Fujiwara, and Y. Nakabeppu., Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen., Nucleic Acids Res., 10.1093/nar/29.11.2349, 29, 11, 2349-2360, 29:2349-2360., 2001.06.
166. Iida, T., A. Furuta, M. Kawashima, J. Nishida, Y. Nakabeppu, and T. Iwaki., Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors., Neuro-oncol., 10.1215/15228517-3-2-73, 3, 2, 73-81, 3:73-81, 2001.04.
167. Rodriguez, J. J., D. R. Garcia, Y. Nakabeppu, and V. M. Pickel., Enhancement of laminar FosB expression in frontal cortex of rats receiving long chronic clozapine administration., Exp. Neurol., 10.1006/exnr.2000.7612, 168, 2, 392-401, 168:392-401, 2001.04.
168. Rodriguez, J. J., D. R. Garcia, Y. Nakabeppu, and V. M. Pickel., FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration., Synapse, 10.1002/1098-2396(200102)39:2<122::AID-SYN3>3.0.CO;2-R, 39, 2, 122-132, 39:122-132, 2001.02.
169. Fujikawa, K., H. Kamiya, H. Yakushiji, Y. Nakabeppu, and H. Kasai., Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP., Nucleic Acids Res., 10.1093/nar/29.2.449, 29, 2, 449-454, 29:449-454., 2001.01.
170. Liang, R., H. Igarashi, T. Tsuzuki, Y. Nakabeppu, M. Sekiguchi, K. S. Kasprzak, and Y. H. Shiao., Presence of potential nickel-responsive element(s) in the mouse MTH1 promoter., Ann. Clin. Lab. Sci., 31, 1, 91-98, 31:91-98, 2001.01.
171. Ito, M., M. Akechi, R. Hirose, M. Ichimura, N. Takamatsu, P. Xu, Y. Nakabeppu, S. Tadayoshi, K. Yamamoto, and K. Yoshioka., Isoforms of JSAP1 scaffold protein generated through alternative splicing., Gene, 10.1016/S0378-1119(00)00335-8, 255, 2, 229-234, 255:229-234, 2000.09.
172. Shimokawa, H., Y. Fujii, M. Furuichi, M. Sekiguchi, and Y. Nakabeppu., Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein., Nucleic Acids Res., 10.1093/nar/28.17.3240, 28, 17, 3240-3249, 28:3240-3249, 2000.09.
173. Takama, F., T. Kanuma, D. Wang, J. I. Nishida, Y. Nakabeppu, N. Wake, and H. Mizunuma., Mutation analysis of the hMTH1 gene in sporadic human ovarian cancer., Int. J. Oncol., 17, 3, 467-471, 17:467-471, 2000.09.
174. Schwartz, W. J., A. Carpino, Jr., H. O. de la Iglesia, R. Baler, D. C. Klein, Y. Nakabeppu, and N. Aronin., Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus., Neuroscience, 10.1016/S0306-4522(00)00140-8, 98, 3, 535-547, 98:535-547, 2000.06.
175. Miyako, K., C. Takamatsu, S. Umeda, T. Tajiri, M. Furuichi, Y. Nakabeppu, M. Sekiguchi, N. Hamasaki, K. Takeshige, and D. Kang., Accumulation of adenine DNA glycosylase-sensitive sites in human mitochondrial DNA., J. Biol. Chem., 10.1074/jbc.275.16.12326, 275, 16, 12326-12330, 275:12326-12330, 2000.04.
176. Morifuji, M., S. Taniguchi, H. Sakai, Y. Nakabeppu, and M. Ohishi., Differential expression of cytokeratin after orthotopic implantation of newly established human tongue cancer cell lines of defined metastatic ability., Am. J. Pathol., 10.1016/S0002-9440(10)65002-X, 156, 4, 1317-1326, 156:1317-1326, 2000.04.
177. Ohtsubo, T., K. Nishioka, Y. Imaiso, S. Iwai, H. Shimokawa, H. Oda, T. Fujiwara, and Y. Nakabeppu., Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria., Nucleic Acids Res., 10.1093/nar/28.6.1355, 28, 6, 1355-1364, 28:1355-1364, 2000.03.
178. Inoue, R., M. Abe, Y. Nakabeppu, M. Sekiguchi, T. Mori, and T. Suzuki., Characterization of human polymorphic DNA repair methyltransferase. deficient mice., Pharmacogenetics, 10.1097/00008571-200002000-00008, 10, 1, 59-66, 10:59-66, 2000.02.
179. Kawate, H., R. Itoh, K. Sakumi, Y. Nakabeppu, T. Tsuzuki, F. Ide, T. Ishikawa, T. Noda, H. Nawata, and M. Sekiguchi., A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice., Carcinogenesis, 10.1093/carcin/21.2.301, 21, 2, 301-305, 21:301-305, 2000.02.
180. Ohyagi, Y., T. Yamada, K. Nishioka, N. J. Clarke, A. J. Tomlinson, S. Naylor, Y. Nakabeppu, J. Kira, and S. G. Younkin., Selective increase in cellular Ab 42 is related to apoptosis but not necrosis., Neuroreport, 10.1097/00001756-200001170-00033, 11, 1, 167-171, 11:167-171., 2000.01.
181. Kalinichev, M., J. S. Rosenblatt, Y. Nakabeppu, and J. I. Morrell., Induction of c-fos-like and fosB-like immunoreactivity reveals forebrain neuronal populations involved differentially in pup-mediated maternal behavior in juvenile and adult rats., J. Comp. Neurol., 10.1002/(SICI)1096-9861(20000103)416:1<45::AID-CNE5>3.0.CO;2-K, 416, 1, 45-78, 416:45-78., 2000.01.
182. Fujii, Y., H. Shimokawa, M. Sekiguchi, and Y. Nakabeppu., Functional significance of the conserved residues for the 23-residue module among MTH1 and MutT family proteins., J. Biol. Chem., 10.1074/jbc.274.53.38251, 274, 53, 38251-38259, 274:38251-38259, 1999.12.
183. Shimura-Miura, H., N. Hattori, D. Kang, K. Miyako, Y. Nakabeppu, and Y. Mizuno., Increased 8-oxo-dGTPase in the mitochondria of substantia nigral neurons in Parkinson's disease., Ann. Neurol., 10.1002/1531-8249(199912)46:6<920::AID-ANA17>3.0.CO;2-R, 46, 6, 920-924, 46:920-924, 1999.11.
184. Oda, H., A. Taketomi, R. Maruyama, R. Itoh, K. Nishioka, H. Yakushiji, T. Suzuki, M. Sekiguchi, and Y. Nakabeppu., Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism., Nucleic Acids Res., 10.1093/nar/27.22.4335, 27, 22, 4335-4343, 27:4335-4343, 1999.11.
185. Ito, M., K. Yoshioka, M. Akechi, S. Yamashita, N. Takamatsu, K. Sugiyama, M. Hibi, Y. Nakabeppu, T. Shiba, and K. I. Yamamoto., JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway., Mol. Cell. Biol., 19, 11, 7539-7548, 19:7539-7548., 1999.11.
186. Fujikawa, K., H. Kamiya, H. Yakushiji, Y. Fujii, Y. Nakabeppu, and H. Kasai., The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein., J. Biol. Chem., 10.1074/jbc.274.26.18201, 274, 26, 18201-18205, 274:18201-18205., 1999.06.
187. Nishioka, K., T. Ohtsubo, H. Oda, T. Fujiwara, D. Kang, K. Sugimachi, and Y. Nakabeppu., Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs., Mol. Biol. Cell, 10, 5, 1637-1652, 10:1637-1652., 1999.05.
188. Hayakawa, H., A. Hofer, L. Thelander, S. Kitajima, Y. Cai, S. Oshiro, H. Yakushiji, Y. Nakabeppu, M. Kuwano, and M. Sekiguchi., Metabolic fate of oxidized guanine ribonucleotides in mammalian cells., Biochemistry, 10.1021/bi982361l, 38, 12, 3610-3614, 38:3610-3614., 1999.03.
189. Ohtsubo, T., O. Matsuda, K. Iba, I. Terashima, M. Sekiguchi, and Y. Nakabeppu., Molecular cloning of AtMMH, an Arabidopsis thaliana ortholog of the Escherichia coli mutM gene, and analysis of functional domains of its product., Mol. Gen. Genet., 259, 6, 577-590, 259:577-590., 1998.10.
190. McGahan, L., A. M. Hakim, Y. Nakabeppu, and G. S. Robertson., Ischemia-induced CA1 neuronal death is preceded by elevated FosB and Jun expression and reduced NGFI-A and JunB levels., Mol. Brain. Res., 10.1016/S0169-328X(98)00039-4, 56, 1-2, 146-161, 56:146-161., 1998.05.
191. Hazell, A. S., L. McGahan, W. Tetzlaff, A. M. Bedard, G. S. Robertson, Y. Nakabeppu, and A. M. Hakim., Immediate-early gene expression in the brain of the thiamine-deficient rat., J .Mol. Neurosci., 10:1-15, 1998.02.
192. Crocker, S. J., M. Morelli, N. Wigle, Y. Nakabeppu, and G. S. Robertson., D1-Receptor-related priming is attenuated by antisense-meditated 'knockdown' of fosB expression., Mol. Brain. Res., 10.1016/S0169-328X(97)00281-7, 53, 1-2, 69-77, 53:69-77, 1998.01.