| 1. |
1. Ishibashi, T., Aramaki, K., Shirane, K., and Matsushima, A., Structural Insight for the different transcriptional properties against the typical estrogen-response element between estrogen receptor alpha and β, Peptide Science 2022, 135-136, 2023.03. |
| 2. |
Jinhyuk Choi, Tae Gyu Oh, Heewon Jung, Kun-Young Park, Hyemi Shin, Taehee Jo, Du-Seock Kang, Dipanjan Chanda, Sujung Hong, Jina Kim, Hayoung Hwang, Moongi Ji, Minkyo Jung, Takashihoji, Ayami Matsushima, Pilhan Kim, Ji Young Mun, Man-Jeong Paik, Sung Jin Cho, In-Kyu Lee, David C Whitcomb, Phil Greer, Brandon Blobner, Mark O Goodarzi, Stephen J Pandol, Jerome I Rotter, Weiwei Fan, Sagar P Bapat, Ye Zheng, Chris Liddle, Ruth T Yu, Annette R Atkins, Michael Downes, Eiji Yoshihara, Ronald M Evans, Jae Myoung Suh, Estrogen-Related Receptor γ maintains pancreatic acinar cell function and identity by regulating cellular metabolism., Gastroenterology, 10.1053/j.gastro.2022.04.013, 2022.04, BACKGROUND & AIMS: Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS: Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histological and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in two distinct human pancreatitis cohorts. RESULTS: Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss-of-ERRγ in primary acini abrogates mRNA expression and protein levels of mitochondrial oxidative phosphorylation (OXPHOS) complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, ER stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared to normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants (SNVs) for ERRγ that associated with chronic pancreatitis. CONCLUSIONS: Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.. |
| 3. |
Hosose, M., Shirane, K., Ishibashi, T., Ito, K., Tagawa, K., and Matsushima, A., Neuropeptide gene expression in the fetal mouse brain exposed to an endocrine-disrupting chemical, Peptide Science 2021, 99-100, 2022.03. |
| 4. |
Ayami Matsushima, Takamasa Teramoto, Yoshimitsu Kakuta, Crystal structure of endocrine-disrupting chemical bisphenol A and estrogen-related receptor γ., Journal of biochemistry, 10.1093/jb/mvab145, 171, 1, 23-25, 2022.01, The human estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor. The ERRγ behaves as a constitutive activator of transcription and plays a key role in controlling mitochondrial energy production and energy metabolism. Bisphenol A (BPA) is used mainly in producing polycarbonate plastics and epoxy resins, but it is known as an endocrine disruptor and strongly binds to ERRγ. We determined the crystal structure of ERRγ in complex with BPA. Our structure revealed the molecular mechanism of BPA recognition by ERRγ, in which BPA is well anchored to its ligand-binding pocket. Our structure is the first report of the complex between a nuclear receptor and endocrine disruptor BPA. This structural analysis had a profound impact on subsequent studies of endocrine disruptors.. |
| 5. |
Daisuke Asai, Naoko Inoue, Makiko Sugiyama, Tsugumi Fujita, Yutaka Matsuyama, Xiaohui Liu, Ayami Matsushima, Takeru Nose, Tommaso Costa, Yasuyuki Shimohigashi, Direct evidence of edge-to-face CH/π interaction for PAR-1 thrombin receptor activation., Bioorganic & medicinal chemistry, 10.1016/j.bmc.2021.116498, 51, 116498-116498, 2021.12, Heptapeptide SFLLRNP is a receptor-tethered ligand of protease-activated receptor 1 (PAR-1), and its Phe at position 2 is essential for the aggregation of human platelets. To validate the structural elements of the Phe-phenyl group in receptor activation, we have synthesized a complete set of S/Phe/LLRNP peptides comprising different series of fluorophenylalanine isomers (Fn)Phe, where n = 1, 2, 3, and 5. Phe-2-phenyl was strongly suggested to be involved in the edge-to-face CH/π interaction with the receptor aromatic group. In the present study, to prove this receptor interaction definitively, we synthesized another series of peptide analogs containing (F4)Phe-isomers, with the phenyl group of each isomer possessing only one hydrogen atom at the ortho, meta, or para position. When the peptides were assayed for their platelet aggregation activity, S/(2,3,4,6-F4)Phe/LLRNP and S/(2,3,4,5-F4)Phe/LLRNP exhibited noticeable activity (34% and 6% intensities of the native peptide, respectively), whereas S/(2,3,5,6-F4)Phe/LLRNP was completely inactive. The results indicated that, at the ortho and meta positions but not at the para position, benzene-hydrogen atoms are required for the CH/π interaction to activate the receptor. The results provided a decisive evidence of the molecular recognition property of Phe, the phenyl benzene-hydrogen atom of which participates directly in the interaction with the receptor aromatic π plane.. |
| 6. |
Masaki Iwamoto, Takahiro Masuya, Mari Hosose, Koki Tagawa, Tomoka Ishibashi, Keitaro Suyama, Takeru Nose, Eiji Yoshihara, Michael Downes, Ronald M Evans, Ayami Matsushima, Bisphenol A derivatives act as novel coactivator-binding inhibitors for estrogen receptor β., The Journal of biological chemistry, 10.1016/j.jbc.2021.101173, 297, 5, 101173-101173, 2021.09, Bisphenol A and its derivatives are recognized as endocrine disruptors based on their complex effects on estrogen receptor (ER) signaling. While the effects of bisphenol derivatives on ERα have been thoroughly evaluated, how these chemicals affect ERβ signaling is less well understood. Herein, we sought to identify novel ERβ ligands using a radioligand competitive binding assay to screen a chemical library of bisphenol derivatives. Many of the compounds identified showed intriguing dual activities as both ERα agonists and ERβ antagonists. Docking simulations of these compounds and ERβ suggested that they bound not only to the canonical binding site of ERβ but also to the coactivator binding site located on the surface of the receptor, suggesting that they act as coactivator-binding inhibitors (CBIs). Receptor-ligand binding experiments using WT and mutated ERβ support the presence of a second ligand-interaction position at the coactivator-binding site in ERβ, and direct binding experiments of ERβ and a coactivator peptide confirmed that these compounds act as CBIs. Our study is the first to propose that bisphenol derivatives act as CBIs, presenting critical insight for the future development of ER signaling-based drugs and their potential to function as endocrine disruptors..  |
| 7. |
Tagawa, K., Suyama, K., Kesamaru, H., Masuya, T., Nose, T., Matsushima, A., Design and synthesis of a universal coactivator peptide binding to the estrogen receptor and Nurr1, Peptide Science 2020, 123-124, 2021.03. |
| 8. |
Keitaro Suyama, Shuhei Kaneko, Hitoshi Kesamaru, Xiaohui Liu, Ayami Matsushima, Yoshimitsu Kakuta, Takashi Okubo, Kazumi Kasatani, Takeru Nose, Evaluation of the Influence of Halogenation on the Binding of Bisphenol A to the Estrogen-Related Receptor γ, Chemical Research in Toxicology, 10.1021/acs.chemrestox.9b00379, 33, 4, 889-902, 2020.04, Halogenation of organic compounds is one the most important transformations in chemical synthesis and is used for the production of various industrial products. A variety of halogenated bisphenol analogs have recently been developed and are used as alternatives to bisphenol A (BPA), which is a raw material of polycarbonate that has adverse effects in animals. However, limited information is available on the potential toxicity of the halogenated BPA analogs. In the present study, to assess the latent toxicity of halogenated BPA analogs, we evaluated the binding and transcriptional activities of halogenated BPA analogs to the estrogen-related receptor γ(ERRγ), a nuclear receptor that contributes to the growth of nerves and sexual glands. Fluorinated BPA analogs demonstrated strong ERRγbinding potency, and inverse antagonistic activity, similar to BPA. X-ray crystallography and fragment molecular orbital (FMO) calculation revealed that a fluorine-substituted BPA analog could interact with several amino acid residues of ERRγ-LBD, strengthening the binding affinity of the analogs. The ERRγbinding affinity and transcriptional activity of the halogenated BPAs decreased with the increase in the size and number of halogen atom(s). The IC50 values, determined by the competitive binding assay, correlated well with the binding energy obtained from the docking calculation, suggesting that the docking calculation could correctly estimate the ERRγbinding potency of the BPA analogs. These results confirmed that ERRγhas a ligand binding pocket that fits very well to BPA. Furthermore, this study showed that the binding affinity of the BPA analogs can be predicted by the docking calculation, indicating the importance of the calculation method in the risk assessment of halogenated compounds.. |
| 9. |
Hirofumi Ohga, Fumiko Akase, Ryo Sakanoue, Ayami Matsushima, Kohei Ohta, Michiya Matsuyama, Alanine scanning and characterization of core peptides in Scombridae fish family for construction of Kiss1 super analog, General and Comparative Endocrinology, 10.1016/j.ygcen.2019.113356, 288, 2020.03, Chronic Kiss1 administration strongly promotes gonadal development in immature chub mackerel (cm) (Scomber japonicus). Here, we performed an Alanine scanning (Ala-scanning) of Kiss1 to determine its key residues. Additionally, we examined functional peptides from 16 Scombridae species to develop maturation-inducing super-analogs that can be used universally in Scombridae species. In the Ala-scanning of Kiss1-15 (QDMSSYNFNSFGLRY), substitution of Gln1 and Asp2 did not affect agonistic activity. This suggests that peptides could be downsized. Furthermore, it is possible that Phe8 can be substituted by unnatural amino acids that are difficult to degrade. In molecular cloning, only Scomber showed a 16-residue form as a putative mature peptide. The other genera, did not have a His residue at the N-terminal, which indicated that the functional peptide was 15 residues and the second and third residues from the N-terminal showed variation between interspecies. Next, we examined the binding affinity of various synthetic Kiss1 core peptides in Scombridae interspecies using an SRE-Luc reporter system. We cloned Kiss1 receptors (KissR1) from bluefin tuna (bft) (Thunnus orientalis) and Japanese Spanish mackerel (jsm) (Scomberomorus niphonius) for the first time. In binding affinity with cmKissR1, bftKissR1, and jsmKissR1, the species specificity of the second residue from the N-terminus in each ligand could be ignored, but the difference in the third residue strongly affected receptor binding. Scombridae species possess the same Kiss1 system but the structure of the functional peptide might be species-specific.. |
| 10. |
Takahiro Masuya,Masaki Iwamoto, Xiaohui Liu, Ayami Matsushima, Discovery of novel oestrogen receptor α agonists and antagonists by screening a revisited privileged structure moiety for nuclear receptors, Scientific reports, 10.1038/s41598-019-46272-y, 9, 1, 2019.12, Bisphenol A (BPA) is used as an industrial raw material for polycarbonate plastics and epoxy resins; however, various concerns have been reported regarding its status as an endocrine-disrupting chemical. BPA interacts not only with oestrogen receptors (ERs) but constitutive androstane receptor, pregnane X receptor, and oestrogen-related receptor γ (ERRγ); therefore, the bisphenol structure represents a privileged structure for the nuclear-receptor superfamily. Here, we screen 127 BPA-related compounds by competitive-binding assay using [3H]oestradiol and find that 20 compounds bind to ERα with high affinity. We confirm most of these as ERα agonists; however, four compounds, including bisphenol M and bisphenol P act as novel antagonists. These structures harbour three benzene rings in tandem with terminal hydroxy groups at para-positions, with this tandem tri-ring bisphenol structure representing a novel privileged structure for an ERα antagonist. Additionally, we perform an ab initio calculation and develop a new clipping method for halogen bonding or non-covalent interaction using DV-Xα evaluation for biomolecules.. |
| 11. |
Xiaohui Liu, Hiroki Sakai, Mitsuhiro Nishigori, Keitaro Suyama, Tasuku Nawaji, Shin Ikeda, Makoto Nishigouchi, Hiroyuki Okada, Ayami Matsushima, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi, Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors, Toxicology and Applied Pharmacology, 10.1016/j.taap.2019.114610, 377, 2019.08, An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERβ, ERRγ, and GR, with IC50 values of 3.3–73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARβ, RARγ, and VDR. PPARγ, RORα, RORβ, RORγ, RXRα, RXRβ, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERβ, ERα, CAR, GR, PXR, PR, AR, LXRβ, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects.. |
| 12. |
Masuya, T., Tada, Y., Lui, A., and Matsushima, A, Evaluation of the binding ability of an orphan nuclear receptor nurr1 to synthetic peptides., Peptide Science 2018,, 113, 2019.03. |
| 13. |
Ayami Matsushima, Jun Sese, Kanako O. Koyanagi, Biosynthetic Short Neuropeptides
A Rational Theory Based on Experimental Results for the Missing Pain-Relief Opioid Endomorphin Precursor Gene, ChemBioChem, 10.1002/cbic.201900317, 20, 16, 2054-2058, 2019.01, Endomorphins are neuropeptides that bind strongly to μ-opioid receptors and are considered to play important roles in pain modulation and other biological functions. Two endomorphins have been identified, to date, endomorphine-1 and -2; both are tetrapeptides and differ by only a single amino acid in the third position. Both peptides were isolated from bovine brains; however, their precursor genes have not been identified. In this study, a nucleotide sequence corresponding to the endomorphin-1 peptide in an expressed sequence tag database has been found and a preproendomorphin-like precursor peptide from human brain complementary DNA (cDNA) has been cloned. The cDNA consists of nucleotide sequences of two already annotated predicted genes, and the putative peptide differs by one amino acid from the isolated endomorphin peptides. It is proposed herein that there is the possibility of unknown short proteins or peptide precursors being missed by automated gene prediction programs based on similarities of known protein sequences. A novel concept of how to produce endomorphins from a similar peptide is described. The oxidatively modified base might provide a clue for understanding discrepancies between nucleotide sequences on the genome and those on cDNAs.. |
| 14. |
Matsushima, A., A Novel Action of Endocrine-Disrupting Chemicals on Wildlife; DDT and Its Derivatives Have Remained in the Environment, Int. J. Mol. Sci., DOI:10.3390/ijms19051377, 19, 5, e1377, 2018.04. |
| 15. |
Sugiyama, M., Fujita, T., Liu, X., Yutaka, M., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y., Phe 2715.39 of Thronbin Receptor PAR-1 is a specific target of Phe-2-phenl group of its tethered ligand, Peptide Science 2017, 95, 2018.03. |
| 16. |
Liu, X., Nakagawa, H., Sugiyama, M., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y., Homodimer function of human nuclear receptor ERRa evidenced using a-helix peptides in the dimer interface, Peptide Science 2017, 191, 2018.03. |
| 17. |
Liu, X., Shimohigashi, M., Sugiyama, M., Matsushima, A., and Shimohigashi, Y., Mutual co-work between nuclear receptor ERa and ERRg requires their homodimerization, Peptide Science 2017, 199, 2018.03. |
| 18. |
Matsushima, A., Nishiimura, H., Matsuyama, Y., Liu, X., and Shimohigashi. Y., Docking simulation to elucidate the labeled cysteine residue of the nociception receptor ORL1 using a Cys(Npys)-containing peptide ligand, Peptide Science 2016, 88, 2017.03. |
| 19. |
Structure-function studies between the hormone-disrupting chemical bisphenols and the nuclear receptors. |
| 20. |
Xiaohui Liu, Hirokazu Nishimura, Akina Fujiyama, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, α-Helix-peptides comprising the human nuclear receptor ERRγ competitively provoke inhibition of functional homomeric dimerization, Biopolymers, 10.1002/bip.22795, 547-554, 2016.11, Estrogen-related receptor γ (ERRγ) is a constitutively active nuclear receptor functioning as a transcription factor. ERRγ binds to a single half site designated as ERRE that has only a single DNA-binding motif. However, with regard to the subunit structure, it remains a matter of controversy whether ERRγ binds as a monomer or dimer. Because the ligand-binding domain (LBD) of ERRγ was in a homodimer form in its X-ray crystal structure, the peptide fragments present in the dimer interfaces would perturb or destabilize the dimer structure by inhibiting the mutual interaction among ERRγ molecules. Thus, to demonstrate the essential homodimer structure of ERRγ, we utilized the peptides corresponding to the α-helix peptides 7 (H7), H9, and H10/11 in order to test such inhibitor activity. These selections were done based on a structural analysis of the X-ray crystal structures of ERRγ-LBD, which forms a head-to-head dimer structure. Peptides were evaluated by means of a luciferase reporter gene assay, in which ERRγ exhibited a high constitutive activity with no ligand. When the peptide was expressed in the HeLa cells together with ERRγ, these peptides clearly showed a concentration-dependent activity inhibition, indicating that ERRγ is indeed homodimerized as required for DNA transcription activity. The present results strongly suggest that human nuclear receptor ERRγ functions as a genuine homomeric dimer with symmetrical dimeric interface regions.. |
| 21. |
Ayami Matsushima, Hiroyuki Nishimura, Yutaka Matsuyama, LIU XIAOHUI, Tomasso Costa, Yasuyuki Shimohigashi, Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol-activated Cys(Npys)-containing peptide ligands, Biopolymers Peptide Science, 10.1002/bip.22792., 2016.03. |
| 22. |
Saya Sakito, LIU XIAOHUI, Akina Fujiyama, Ayami Matsushima, Yasuyuki Shimohigashi, Do the estrogen receptors function as a homodimer? experimental validation of homodimerization by inhibitory peptides., Peptide Science 2015, 335-336, 2016.03. |
| 23. |
Yudai Motomatsu, Hirokazu Nishimura, Yutaka Matsuyama, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, ORL1 Nociceptin receptor response of opioid peptides derived from proenkephalin precursor protein., Peptide Science 2015, 181-182, 2016.03. |
| 24. |
Makiko Sugiyama, Yudai Motomatsu, Yutaka Matsuyama, Syota Kajiiyama, Tomonori Kameda, Tatsuya Saito, Eriko Uchimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, SCN Circadian rhythm signal transduction neuropeptides evoke hypoactive phenotype differently in male and female mice., Peptide Science 2015, 53-54, 2016.03. |
| 25. |
Yutaka Matsuyama, Hirokazu Nishimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, Comparative analysis of the ligand binding domain secondary structures of human nuclear receptors., Peptide Science 2015, 337-338, 2016.03. |
| 26. |
Asuka Tokumaru, Ayaka Matsuo, Syogo Umeno, Yutaka Matsuyama, Masayoshi Nakamura, Tatsuya Saito, Miho Sumiyoshi, LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, Expression analysis of neuropeptide PDF mRNA in the hypoactive and hyperactive fruit flies Drosophila melanogaster., Peptide Science 2015, 317-318, 2016.03. |
| 27. |
Yuuki Takesue, Hirokazu Nishimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, Functional role of the Phe-Phe stacking microswitch in the ORL1 nociceptin receptor activation., Peptide Science 2015, 147-148, 2016.03. |
| 28. |
Ayami Matsushima, Hirokazu Nishimura, LIU XIAOHUI, Yuuki Takesue, Yutaka Matsuyama, Yasuyuki Shimohigashi, Comprehensive structural analysis of the nociceptin ORL1 receptor by means of virtual and experimental Ala-scanning combinated methods., Peptide Science 2015, 149-150, 2016.03. |
| 29. |
劉 暁輝、松島綾美、下東康幸, 乳がん細胞における内分泌撹乱物質ビスフェノールのエストロゲン受容体応答, 月刊 細胞 the cell（ニューサイエンス）, 2016.03. |
| 30. |
Yutaka Matsuyama, Hirokazu Nishimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, Structural and molecular evolutionary analysis of the ligand-binding domain of forty-eight human nuclear receptors, Peptide Science 2014, 459-460, 2015.03. |
| 31. |
Ayami Matsushima, Kanako T. Koyanagi, Hirokazu Nishimura, Shogo Inamine, Yuudai Motomatsu, Yasuyuki Shimohigashi, An in silico genomic search of endomorphin-like opioid
peptides, Peptide Science 2014, 281-282, 2015.03. |
| 32. |
Hirokazu Nishimura, Jinglan Li, Kaname Isozaki, Yuuki Takesue, LIU XIAOHUI, Miki Shimohigashi, Shogo Inamine, Ayami Matsushima, Yasuyuki Shimohigashi, The molecular switching of ORL1 nociceptin receptor in activation/inactivation., Peptide Science 2014, 201-202, 2015.03. |
| 33. |
Makiko Sugiyama, Shota Kajiyama, Tatsuya Nakamura, Eri Uchimura, Yudai Motomatsu, Ayaka Matsuo, Ayami Matsushima, Yasuyuki Shimohigashi, Alternative polyadenylation analyses of neuropeptide genes in bisphenol A-exposed hypoactive mouse brain., Peptide Science 2014, 345-346, 2015.03. |
| 34. |
Syotaro Umeno, Ayaka Matsuo, Yutaka Matsuyama, Masayuki Nakamura, Keita Koga, LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, Bisphenol A-induced substantial peak decay of Drosophila circadian neuropeptide hugin mRNA expression., Peptide Science 2014, 41-42, 2015.03. |
| 35. |
LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, A characteristic back support structure in the bisphenol A-binding pocket in the human nuclear receptor ERR, PLoS ONE, 10.1371/journal.pone.0101252, 9, e101252, 2014.06. |
| 36. |
Jinglan Li, Hirokazu Nishimura, Ayami Matsushima, Yasuyuki Shimohigashi, N-Methylthioacetylation of RYYRIK-NH2 with enhanced specific binding affinity and high antagonist activity for nociceptin ORL1 receptor, Bioorg. Med. Chem., 10.1016/j.bmc.2014.09.049, 22, 5712-5716, 2014.05. |
| 37. |
Shogo Inamine, Hirokazu Nishimura, Jinglan Li, Kaname Isozaki, Ayami Matsushima, Tomasso Costa, Yasuyuki Shimohigashi, Tritium-labelled isovaleryl-RYYRIK-NH2 as potential antagonist probe for ORL1 nociceptin receptor, Bioorg. Med. Chem., 10.1016/j.bmc.2014.09.049, 22, 5902-5909, 2014.05. |
| 38. |
Yuudai Motomatsu, Hirokazu Nishimura, Yuka Matsumoto, Shoji Inamine, Yumi Kuramitsu, Ayami Matsushima, Yasuyuki Shimohigashi, Specific Role of Phe Residues in Opioid Peptide Met-enkephalin- Arg-Phe in Binding to All Three Opioid Receptors., Peptide Science 2013, 317-318, 2014.03. |
| 39. |
Yumi Kuramitsu, Hirokazu Nishimura, Ryo Nakamura, Keitaro Suyama, Takeru Nose, Ayami Matsushima, Yasuyuki Shimohigashi, Structure-activity Studies on the Halogenated Phe-containing Neuropeptide Substance P Analogs., Peptide Science 2013, 319-320, 2014.03. |
| 40. |
Hirokazu Nishimura, Jinglan Li, Kaname Isozaki, Yukinori Abe, Shogo Inamine, Ayami Matsushima, Tomasso Costa, Yasuyuki Shimohigashi, Specific Role of Phe Residues in Opioid Peptide Met-enkephalin- Arg-Phe in Binding to All Three Opioid Receptors., Peptide Science 2013, 333-334, 2014.03. |
| 41. |
Ayami Matsushima, Hirokazu Nishimura, Shogo Inamine, Yasuyuki Shimohigashi, Multiple and Simultaneous Cys→Ala Mutations of ORL1 Nociceptin Receptor to Identify the Affinity Binding site of Cys(Npys)-Elongated RYYRIK Peptide Antagonist., Peptide Science 2013, 457-478, 2014.03. |
| 42. |
LIU XIAOHUI, Hirokazu Nishimura, Akina Fujiyama, Ayami Matsushima, Yasuyuki Shimohigashi, Constitutive α-Helix-peptides Required for Functional Dimerization of Estrogen-related Receptor γ (ERRγ)., Peptide Science 2013, 294-295, 2014.03. |
| 43. |
Makiko Sugiyama, Ayaka Matsuo, Tatsuya Saito, Eri Uchimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, Expression and Mutation Analyses of Brain Neuropeptide Genes of Rndocrine-disrupting Bisphenol A-exposed Hypoactive Mouse., Peptide Science 2013, 453-454, 2014.03. |
| 44. |
Syotaro Umeno, Ayaka Matsuo, Yutaka Matsuyama, Yukimasa Takeda, Miho Sumiyoshi, LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, Influence Analysis of the Circadian Evening Pacemaker Neuropeptide hugγ Gene in the Bisphenol A-exposed Fruit Fly Drosophila Brain., Peptide Science 2013, 455-456, 2014.03. |
| 45. |
Ayaka Matsuo, Syotaro Umeno, Yutaka Matsuyama, Masayuki Nakamura, Yukimasa Takeda, Miho Sumiyoshi, LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, Bisphenol A-induced Epigenetic Mutations in Circadian Pacemaker Neuropeptide mRNAs of Hyperactive Drosophila Fruit Flies., Peptide Science 2013, 457-458, 2014.03. |
| 46. |
Yutaka Matsuyama, LIU XIAOHUI, Hirokazu Nishimura, Ayami Matsushima, Yasuyuki Shimohigashi, Three-dimensional Docking Modeling to Human Nuclear Receptors for Exploration of Bisphenol-A Targeting Receptors. , Peptide Science 2013, 459-460, 2014.03. |
| 47. |
Yuuki Takesue, Hirokazu Nishimura, LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, GPCR functional role of Phe-269 and Phe-221 in the molecular switching of ORL1 nociceptin receptor activation., Peptide Science 2014, 203-204, 2014.03. |
| 48. |
Yuudai Motomatsu, Hirokazu Nishimura, Yuka Matsumoto, Yuki Kuramitsu, Shogo Inamine, Ayami Matsushima, Yasuyuki Shimohigashi, Receptor selectivity and specificity of a series of opioid peptides latent in the proenkephalin precursor protein., Peptide Science 2014, 205-206, 2014.03. |
| 49. |
LIU XIAOHUI, Ayami Matsushima, Yasuyuki Shimohigashi, A novel method to identify and Quantify the coactivator proteins that couple with human nuclear receptor: the use of interacting interface a-helix peptide for quantative inhibition, Peptide Science 2014, 347-348, 2014.03. |
| 50. |
LIU XIAOHUI, Akina Fujiyama, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, α-Helix-Peptides Composing the human nuclear receptor ERRγ competitively provoke inhibition of functional homomeric dimerization., Biopolymers Peptide Science, 10.1002/bip.22795., 2014.03. |
| 51. |
Ayami Matsushima, Hirokazu Nishimura, Shogo Inamine, Yasuyuki Shimohigashi, Identification of affinity binding site of Cys(Npys)-elongated RYYRIK peptide antagonist by means of Cys→Ala mutated ORL1 nociceptin receptors., Peptide Science 2012, 115-118, 2013.03, We have previously developed a peptidic affinity ligand for the ORL1 nociceptin receptor. It contains Cys(Npys) instead of isovareroyl of a pure antagonist peptide isovareroyl-RYYRIK-NH2. In this study, in order to identify the exact binding site of Cys(Npys), we performed affinity labeling experiments of a series of Cys→Ala mutated ORL1 receptors. A certain number of mutant receptors showed labeling effectiveness weaker than wild type receptor, suggesting that the recepor Cys was labeled by Cys(Npys)-RYYRIK-NH2.. |
| 52. |
Shogo Inamine, Hirokazu Nishimura, Jinglan Li, Ayami Matsushima, Tomasso Costa, Yasuyuki Shimohigashi, Two different binding modes of peptide library-based antagonist acyl-RYYRIK amide in the orl1 nociceptin receptor., Peptide Science 2012, 229-230, 2013.03. |
| 53. |
Yumi Kuramitsu, Hirokazu Nishimura, Ryo Nakamura, Keitaro Suyama, Ayami Matsushima, Takeru Nose, Yasuyuki Shimohigashi, High-precision binding assay procedure of tachykinin receptor NK-1 for highly potent Substance P analogs., Peptide Science 2012, 213-214, 2013.03. |
| 54. |
Hirokazu Nishimura, Shogo Inamine, Jinglan Li, Ayami Matsushima, Yasuyuki Shimohigashi, Exploration of pharmacological chaperone for rescue of misfolded and/or unfolded ORL1 nociceptin receptor proteins., Peptide Science 2012, 115-118, 2013.03. |
| 55. |
Ayaka Matsuo, Masayuki Nakamura, Yukimasa Takeda, Yutaka Matsuyama, Miho Sumiyoshi, LIU XIAOHUI, Ayami Matsushima, Miki Shimohigashi, Yasuyuki Shimohigashi, The impact of bisphenol A-feeding on the Drosophila neuropeptide PDF mRNA structure., Peptide Science 2012, 115-118, 2013.03. |
| 56. |
Kanako Nishio, Hirokazu Nishimura, Keiichiro Suyama, Keita Koga, Ayami Matsushima, Takeru Nose, Yasuyuki Shimohigashi, Halogenated Phe-containing endomorphin-2 analogs with mixed agonist and antagonist activities., Peptide Science 2012, 25-26, 2013.03. |
| 57. |
Ayaka Matsuo, Hirokazu Nishimura, Ryo Nakamura, Keita Koga, Miho Sumiyoshi, Ayami Matsushima, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi, Structural characteristics of Thr-Gly dipeptide repeat in the Drosophila clock protein PERIOD., Peptide Science 2012, 351-352, 2013.03. |
| 58. |
Ayami Matsushima, Kerrianne Ryan, Yasuyuki Shimohigashi, Ian A. Meinertzhagen, An endocrine disruptor, bisphenol A, affects development in the protochordate Ciona intestinalis, Environ. Pollut., 10.1016/j.envpol.2012.10.015, 173, 257-263, 2013.02. |
| 59. |
Liu X, Matsushima A, Nakamura M, Costa T, Nose T, Shimohigashi Y, Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol A in the human nuclear receptor estrogen-related receptor γ., J. Biochem. , 10.1093/jb/mvs008, 151, 4, 403-415, 2012.04, Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen-related receptor γ (ERRγ), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRγ ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRγ receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol-hydroxyl↔Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRγ.. |
| 60. |
Nishimura, H., Li, J., Isozaki, K., Abe, Y., Inamine, S., Matsushima, A., Nose, T., Costa, T., and Shimohigashi Y., Structural essentials of hyperalgesic nococeptin ORL1 receptor for ligand binding and receptor activation., Peptide Science 2011, 33-34, 2012.03, heptapeptide nociceptin is an endogeneous ligand of the class A GPCR named opioid receptor-like 1 (ORL1) receptor. Because of its unique physiological functions, it is crucial to elucidate the structure activity relationships between the lidand nociceptin and the receptor ORL1. In the present study, we thus employed the point mutagenesis technique to complete on--by-one Ala-scannning of all the amino acid residues(161 in total) of the entire seven transmembrane domains including helix domain #8. . |
| 61. |
Nishio, K., Hishimura, H., Suyama, K., Abe, Y., Matsushima, A., Nose, T., and Shimohigashi Y., Effects ofthe halogenation of Phe-phenyl group of two consecutive residues in endomorphin-2 on the interaction with the μ–opioid receptors., Peptide Science 2011, 171-172 , 2012.03, The phenyl group of two consequtive Phe residues in endomorphin-2 (EM-2) are essential for the peptide to interact with mu-opioid receptor. To elucidate their structural requirements for receptor binding, we synthesized a series of EM-2 analogs containing a halogenated Phe residues at position either 3 or 4. As a result, [(0-Cl, Br, or I)Phe3]EM2 was found to be several times more potent then the parent EM-2. Restriction of Phe side chain and electrostatic halogen bond was supposed as possible cause of this activity enhancement. . |
| 62. |
Inamine, S., Nishimura, H., Li, J., Matsushima, A., Nose, T., Costa, T., and Shimohigashi Y., Receptor Binding Characteristics of Tritium-labeled Pure antagonist Peptide for Hyperalgesic nociceptin ORL1 receptor., Peptide Science 2011, 183-184, 2012.03, Iso Va-RYYRIK-NH2 is a highly specific antagonist of the ORL1 (opioid receptor like 1) receptor. For better design of effective ORL1 antgonist, a potencial target of therapeutics as analgesic and anti-neuropathy drugs, a specific radiolabeld antagonist is required. In the present study, we developed a tritium-labeled isoVa-RYYRIK-NH2 derivative, and evaluated its receptor binding characteristics for ORL1.. |
| 63. |
Matsushima, A., Nishimura, H., Inamine, S., Uemura, S., and Shimohigashi Y., Affinity Labeling of the ORL1 Nociceptin Receptor by Cys(Npys)-Elongated RYYRIK Peptide Antagonist, Peptide Science 2011, 179-180, 2012.03, Affinity-labeling techniques based on the specific recognition of ligand-receptor interactions are extremely important and useful methods in receptor biochemistry. In this study, we introduced SNpys group into an antagonist peptide of the ORL1 receptor. Affinity labeling experiments were performed in comparison with non-specific thiol alkylation reagent N-ethylmaleimide, and Cys(Npys)- RYYRIK-NH2 was found indeed to affinity-label specifically the ORL1 receptor. |
| 64. |
Yutaka Matsuyama, LIU XIAOHUI, Hirokazu Nishimura, Ayami Matsushima, Takeru Nose, Yasuyuki Shimohigashi, Bisphenol-binding pocket of constitutively active nuclear receptor CAR: Docking modeling for close-packing., Peptide Science 2012, 115-118, 2012.03. |
| 65. |
Matsushima, A., Nishimura, H., Inamine, S., Uemura, S., Shimohigashi, Y., Capturing of the free cysteine residue in the ligand-binding site by affinity labeling of the ORL1 nociceptin receptor., Bioorg. Med. Chem., 10.1016/j.bmc.2011.10.024 , 19, 7597–7602, 2011.09, All of the δ, μ, and κ opioid receptors have a free thiol group of the Cys residue in the ligand-binding site, although its functional role is not yet known. In order to examine whether or not a similar Cys is also present in the ORL1 nociceptin receptor, we attempted to identify it by affinity labeling using a specific antagonist peptide. We first treated ORL1-expressing COS-7 cell membrane preparations with the thiol-alkylation reagent N-ethylmaleimide (NEM) to perform a binding assay using [(3)H]nociceptin as a tracer and nociceptin, an ORL1 agonist, or Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2), a nociceptin/ORL1 antagonist, as a competitor. It was suggested that ORL1 has a free Cys in its ligand-binding site, since the NEM treatment reduced the population of ligand-binding sites. This was further confirmed by affinity labeling using Cys(Npys)-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) with the SNpys group that can react with a free thiol group, resulting in the formation of a disulfide bond. This affinity labeling was approximately 23 times more specific than NEM alkylation. The results revealed that the ORL1 nociceptin receptor does contain a free Cys residue in the ligand-binding site.. |
| 66. |
Nishimura, H., Li, J., Inokuchi, N., Koikawa, S., Matsushima, A., Nose, T., Costa, T. and Shimohigashi, Y., The Trp residue of opioid receptor TM5 present at the cell membrane interface is a molecular anchor for full activation., Peptide Science 2010, 2011.03. |
| 67. |
Inamine, S., Li, J., Nishimura, H., Matsushima, A., Nose, T., Costa, T. and Shimohigashi, Y., Exploration of the binding site of ORL1 nociceptin receptor antagonist., Peptide Science 2010, 2011.03. |
| 68. |
Hassaneen, E., El-Din Sallam, A., Abo-Ghalia, A., Moriyama, Y., Karpova, S.G., Abdelsalam, S., Matsushima, A., Shimohigashi, Y., and Tomioka, K., Pigment-Dispersing Factor Affects Nocturnal Activity Rhythms, Photic Entrainment and the Free-Running Period of the Circadian Clock in the Cricket Gryllus bimaculatus, J. Biol. Rhythm, 26, 3-13, 2011.01. |
| 69. |
Arase, S., Ishii, K., Igarashi, K., Aisaki, K., Yoshio, Y., Matsushima, A., Shimohigashi ,Y., Arima, K., Kanno, J., Sugimura, Y., Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus. , Bio. Reprod., 84, 734-742, 2011.01. |
| 70. |
Liu, X., Matsushima, A., Okada, H., and Shimohigashi, Y., Distinction of the binding modes for human nuclear receptor ERRγ between bisphenol A and 4-hydroxytamoxifen, J. Biochem, 148, 247–254, 2010.05. |
| 71. |
Matsushima, A., Liu, X., Okada, H., Shimohigashi, M., and Shimohigashi, Y, Bisphenol AF is a Full Agonist for the Estrogen Receptor ERα, but a Highly Specific Antagonist for ERβ., Environ. Health Perspect., 2010.04. |
| 72. |
Nishimura, H., Li, J., Inokuchi, N., Koikawa, A., Matsuhima, A., Nose, T., Costa, T., and Shimohigashi, Y., The functional role of Trp present at the cell membrane interface in the opioid receptor activation., Peptide Science 2009, 23–24, 2010.03. |
| 73. |
Horiuchi, Y., Matsushima, A., and Shimohigashi, Y., The direct measure of intermolecular interaction of prion protein N-terminal octapeptide repeats by the quarts crystal microbalance (QCM)., Peptide Science 2009, 207–208, 2010.03. |
| 74. |
Horiuchi, Y., Matsushima, A., and Shimohigashi, Y., Shimohigashi, M., Itoh, T.Q., Honda, T., Saito, M., Koga, K., Takahashi, K., Matsushima, A., Ueda, R., Tanimura T., Shimohigashi, Y., and Matsumoto A., Peptide Science 2009, 217–218, 2010.03. |
| 75. |
Li, J., Isozaki, K., Matsushima, A., Nose, T., Costa, T., and Shimoohigashi, Y., Structure-function analysis of nociceptin receptor ORL1 by the site-directed mutagenesis, Peptide Science 2009, 219–220, 2010.03. |
| 76. |
Sato, K., Horiuchi, Y., Matsushima, A., and shimohigashi, Y., The preparation and purification of prion protein N-terminal domain with fluctuations in the number of octapeptide repeat, Peptide Science 2009, 433–434 , 2010.03. |
| 77. |
Liu, X., Matsushima, A., Okada, H., and Shimohigashi, Y., Functional role of the C-terminal Helix 12 peptide in the receptor activation mechanism of estrogen-related receptor γ (ERRγ)., Peptide Science 2009, 435–436, 2010.03. |
| 78. |
Nishimura, H., Li, J., Isozaki, K., Okada, K., Matsushima, A., Nose, T., Costa, T., and Shimohigashi, Y., Discriminatory synergistic effect of Trp-substitutions in superagonist [(Arg/Lys)14, (Arg/Lys)15]nociceptin on ORL1 receptor binding and activation., Bioorg. Med. Chem.,, 17,, 5683–5687, 2009.10. |
| 79. |
Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y., Placenta expressing the greatest quantity of bisphenol A receptor ERRγ among the human reproductive tissues: predominant expression of type-1 ERRγ isoform, J. Biochem., , 146, 113-122, 2009.10. |
| 80. |
Isozaki, K., Li, J., Okada, K., Nishimura H., Matsushima, A., Nose, T., Costa, T., Shimohigashi, Y., Spare interactions of highly potent [Arg14,Lys15]nociceptin for cooperative induction of ORL1 receptor activation, Bioorg. Med. Chem., , 17, 7904–7908, 2009.10. |
| 81. |
Matsushima, A., Okada, H., Liu, X., Tokunaga, T., Teramoto, T., Kakuta, Y., Shimohigashi, Y., Induced-fit type ligand binding guided by free-rotatory Leu residue present in the 7th α-helix peptide in the estrogen-related receptor γ (ERRγ), Peptide Science 2008, 521-522, 2009.03. |
| 82. |
Horiuchi, Y., Hattori, E., Yokotani, S., Matsushima, A., and Shimohigashi, Y., Molecular recognition of prion protein via its N-terminal octapeptide repeat Structure, Peptide Science 2008, 513-516, 2009.03. |
| 83. |
Ikeda, S., Matsushim, A., and Shimohigashi, Y., ERα/ERRα Nuclear Receptor Heterodimer Directly Linked by A Flag Peptide., Peptide Science 2008, 511-512, 2009.03. |
| 84. |
Takeda, Y., Liu, X., Sumiyoshi, M., Matsushima, A., Shimohigashi, Y. and Shimohigashi, M., Bisphenol A-specific nuclear receptor ERRγ: structure-function analysis of the two novel isoforms lacking vital peptide fragment in the ligand binding domain, Peptide Science 2008, 517-518, 2009.03. |
| 85. |
Matsushima. A., Teramoto, T., Okada, H., Liu, X., Tokunaga, T., Kakuta, Y., and Shimohigashi, Y., ERRγ tethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner., Biochem. Biophys. Res. Commun., 373, 408-413 (2008), 2008.12. |
| 86. |
Yokotani, S., Nose, T., Horiuchi, Y., Matsushima, A., and Shimohigashi, Y., Radar chart deviation analysis of prion protein amino acid composition defines characteristic structural abnormalities of the N-terminal octapeptide tandem repeat., Protein Peptide Sci., 15, 949-955 (2008), 2008.08. |
| 87. |
Okada, H., Tokunaga, T., Lui, X., Takayanagi, S., Matsushima, A., and Shimohigashi, Y., Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor γ (ERRγ)., Environ. Health Perspect., 116, 32-38 (2008), 2008.01. |
| 88. |
Li, J. Isozaki, K., Okada, K., Matsushima, A., Nose, T., Costa, T., and Shimohigashi, Y., Design Synthesis of Highly Potent Antagonist of ORL1 Nociceptin Receptor., Bioorg. Med. Chem., 16, 2635-2664 (2008), 2008.01. |
| 89. |
Li, J. Isozaki, K., Matsushima, A., Nose, T., Costa, T., and Shimohigashi, Y., Optimization of the N-Terminal Group of Ac-RYYRIK-NH2 as ORL1 Receptor Antagonist, Peptide Science 2007, 257-260 (2008), 2008.01. |
| 90. |
Takeda, Y., Koga, K., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y., The Output Mechanism of Circadian Pacemaker Neuropeptide PDF in the Regulation of Bimodal Locomotor Distribution, Peptide Science 2007, 65-68 (2008), 2008.01. |
| 91. |
Matsushima, A., Koretsune, Y., Kaneki, A., Isozaki, K., Shimohigashi, M., and Shimohigashi, Y., Structural Requirement of Housefly FMRFamide Peptides in Its Receptor Activation., Peptide Science 2007, 313-314 (2008), 2008.01. |
| 92. |
Hattori, E., Yokotani, S., Horiuchi, Y., Matsushima, A., and Shimohigashi, Y., The Effect of Amino Acid Substitution on Oligomerization of Octapeptide Repeat Structure in Prion Protein. , Peptide Science 2007, 239-242 (2008), 2008.01. |
| 93. |
Matsushima, A., Shimohigashi, Y., A strategy to explore the target receptor of endocrine disruptors: Estrogen-related receptor γ (ERRγ) as a genuine acceptor of bisphenol A., Alternatives to Animal Testing and Experimentation.AATEX journal, 14, special issue,, 14, special issue, 495-497, 2008.01. |
| 94. |
Matsushima, A., Kakuta, Y., Teramoto, T., Koshiba, T., Liu, X., Okada, H., Tokunaga, T., Kawabata, S., Kimura, M., and Shimohigashi, Y., Structural Evidence for Endocrine Disruptor Bisphenol A Binding to Human Nuclear Receptor ERRγ, J. Biochem., 142, 517-524 (2007), 2007.10. |
| 95. |
Liu, X., Matsushima, A., Okada, H., Tokunaga, T., Isozaki, K., and Shimohigashi, Y., Receptor binding characteristics of endocrine disruptor bisphenol A: Chief and corroborative hydrogen bonds of bisphenol A phenol-hydroxyl group with Arg316 and Glu275 residues in the human nuclear receptor of estrogen-related receptor γ , FEBS J., 274, 6340-6351 (2007), 2007.10. |
| 96. |
Matsushima, A., Takano, K., Yoshida, T., Takeda, Y., Yokotani, S., Shimohigashi, Y., and Shimohigashi, M., Double-labeled in situ Hybridization Reveals the Lack of Co-localization of mRNAs for the Circadian Neuropeptide PDF and FMRFamide in Brains of the Flies Musca domestica and Drosophila melanogaster, J. Biochem, 141, 867-877 (2007), 2007.06. |
| 97. |
Tokunaga, T., Liu, X., Okada, H., Matsushima, A., Nose, T., Shimohigashi, M., and Shimohigashi, Y., Conformation Change of α-Helix Peptide for Sensing of Deactivation of Nuclear Receptor: Immunoassay Using Polyclonal Antibody Specific for the C-terminal α-Helix 12 of Estrogen-related Receptor γ (ERRγ), Peptide Science 2006, 176, (2006), 2006.12. |
| 98. |
Kaneki, A., Yoshida, T., Isozaki, K., Matsushima A., Shimohigashi, M., and Shimohigashi, Y., Molecular Cloning and in situ Hybridization of Circadian Neuropeptide PDF Receptor in the Fruit Fly Drosophila melanogaster, Peptide Science 2006, 263, (2006), 2006.12. |
| 99. |
Koga, K., Yakayama, Y., Hiramura, D., Takeda, Y., kaneki, A., Matsushima, A., Shimohigashi, Y., and Shimoshigashi, M., Immunological Confirmation of Circadian-related Neuropeptide PDF-Isoform Peptide in the Cricket Gryllus bimaculatus, Peptide Science 2006, 262, (2006), 2006.12. |
| 100. |
Takeda, Y., Sumiyuki, M., Koga, K., Ito, M., Matsushima, A., Shimohigashi, Y., and Shimohigashi, M., Multiple Post-transcriptional Regulations in Circadian Pacemaker Neuropeptide pdf Gene, Peptide Science 2006, 260, (2006), 2006.12. |
| 101. |
Matsushima, A. Koretsune, Y., Kaneki, A. Isozaki, K., Shimohigashi, M., and Shimohigashi, Y., Structure-Activity Studies of FMRFamide-Related Peptides in Activating the Specific Receptor Present in the Housefly Musca domestica, Peptide Science 2006, 174, (2006), 2006.12. |
| 102. |
Takayanagi, S., Tokunaga, T., Liu, X., Okada, H., Matsushima, A., and Shimohigashi, Y., Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor γ (ERRγ) with high cinstitutive activity, Toxicol. Lett., 195, 95-105 , 2006.11. |
| 103. |
Honda, T., Matsushima A., Sumida K., Chuman Y., Sakaguchi K., Onoue H., Meinertzhagen I.A., Shimohigashi Y., and Shimohigashi, M., Structural isoforms of the circadian neuropeptide PDF expressed in the optic lobes of the cricket Gryllus bimaculatus: Immunocytochemical evidence from specific monoclonal antibodies, J. Comp. Neurol., 499, 404-421, 2006.10. |
| 104. |
Honda, T., Matsushima, A., Hiramura, D., Sumida, K., Takeda, Y., Sato, S., Meinertzhagen I.A., Shimohigashi, Y., and Shimohigashi, M.,, Immunological evidences of circadian neuropeptide PDF isoform present at the lamina outer cells and varicose network in the optic lobes of the cricket Gryllus bimaculatus, Peptide Science 2005, 181-184 (2006), 2006.03. |
| 105. |
Matsushima, A., Horiuchi, Y., Yokotani, S., Kawano, M., and Shimohigashi, Y., Specific dimerization of prion protein N-terminal domain, Peptide Science 2005, 457-458 (2006), 2006.03. |
| 106. |
Sato, S., Jonathan C., Corrins, Takeda, Y., Kaneki, A., Matsushima, A., Shimohigashi, Y., and Shimohigashi, M., Identification of novel isoforms of the circadian neuropeptide PDF in the silk moth Bombyx mori and their expression in brain, Peptide Science 2005, 99-100 (2006), 2006.03. |
| 107. |
Okada, H., Tokunaga, T., Shirasu N., Matsushima, A., Nose, T., and Shimohigashi Y.,, a-helix peptides for bio-panning in the phage display method to obtain the antibodies specific for conformation-change nuclear receptors, Peptide Science 2005, 291-294 (2006), 2006.03. |
| 108. |
Koga, K., Sato S., Horiuchi Y., Matsushima, A., and Shimohigashi, Y., Design and synthesis of a-helix peptide binding to prion protein N-terminal octarepeat domain, Peptide Science 2005, 209-210 (2006), 2006.03. |
| 109. |
Horiuchi, Y., Kawano, M., Yokotani, S., Honda, T., Matsushima, A., Nose, T., and Shimohigashi, Y., Structural Characteristics of the N-Terminal Octapeptide Repeat Region of Prion Protein in Self-Polymerization, Peptide Science 2004, 317-318 (2005), 2005.03. |
| 110. |
okotani, S., Matsushima, A., Nose, T., Morishita, F., and Shimohigashi Y., Bioactive Conformation of a D-Trp-Containing Cardioexcitatory Tripeptide Isolated from the Sea Hare Aplysia, Peptide Science 2004, 539-540 (2005), 2005.03. |
| 111. |
Sato, S., Sumida, K., Hiramura, D., Matsushima, A., Tominaga, Y., Shimohigashi, Y., and Shimohigashi, M., cDNA Cloning and mRNA Expression of the Circadian Neuropeptide PDF in the Silk Moth Bombyx mori, Peptide Science 2004, 197-200 (2005), 2005.03. |
| 112. |
Liu, X., Matsushima, A., Shirasu, N., Tominaga, Y., Shimohigashi, M., Shimohigashi, Y., and Nose, T., Structural Characteristics of Drosophila Estrogen-Related Receptor Ligand Binding Domain to Capture the Peptide and Non-peptide Ligands, Peptide Science 2004, 303-304 (2005), 2005.03. |
| 113. |
Takeda, Y., Shirasu, N., Sato, S., Matsushima, A., Chuman, Y., Tominaga, Y., Shimohigashi, M., and Shimohigashi, M., Triplicate Alternative Splicings that Produce Multiple Variants of the PERIOD Protein in the Silk Moth Bombyx mori by Deletion/Insertion of Peptides, Peptide Science 2004, 203-206 (2005), 2005.03. |
| 114. |
Kawano, M., Honda, T., Horiuchi, Y., Yokotani, S., Matsushima, A., Nose, T., and Shimohigashi, Y., Conformation Change-senseing Assay Using Monoclonal Antibody for N-terminal Octapeptide Repreat Region of Prion Protein, Peptide Science 2004, 355-356 (2005), 2005.03. |
| 115. |
Sumida, K., Honda, T., Matsushima, A., Tominaga, Y., Shimohigashi, Y., and Shimohigashi, M., Immunocytochemical Identification of Mature Peptide Formation for the Circadian Neuromodulator PDF in the Housefly Musca domestica, Peptide Science 2004, 347-350 (2005), 2005.03. |
| 116. |
Shimohigasi M., Honda T., Matsushima A., Sumida K., Meinertzhagen, I.A., Shimohigasi Y., and Tominaga Y., Immunocytochemical Studies on the Circadian Neuropeptide PDF in the Cricket Gryllus bimaculatus, Peptide Science 2004, 339-342 (2005), 2005.03. |
| 117. |
Matsushima, S., Yokotani, S., Sato, S., Kaneki, A., Takeda, Y., Chuman, Y., Ozaki, M., Asai, D., Nose, T., Onoue, H., Ito, Y., Tominaga, Y., Shimohigashi, Y., and Shimohigashi, M., Molecular Cloning and Circadian Expression Profile of Pacemaker Neuropeptide PDF in Diptera, Lett., Peptide Sci., 10, 419-430 (2003), 2005.01. |
| 118. |
Y. Takeda, Y. Chuman, N. Shirasu, S. Sato, A. Matsushima, A. Kaneki, Y. Tominaga, Y. Shimohigashi, and M. Shimohigashi, Structural Analysis and Identification of Novel Isoforms of the Circadian Clock Gene period in the Silk Moth Bombyx mori, Zool. Sci., 10.2108/zsj.21.903, 21, 9, 903-915, 21, 903-915 (2004)., 2005.01. |
| 119. |
Matsushima ., Yokotani, S., Koretsune, Y., Meinertzhagen, I.A., Tominaga, Y., Shimohigashi, M., and Shimohigashi, Y., FMRFamide-Related Peptides in the Nervous System of the Housefly Musca domestica: cDNA Cloning and Actions on Clam Heart Contraction, Peptide Science 2004, 157-160 (2005)., 2005.01. |
| 120. |
A. Matsushima, S. Sato, Y. Chuman, Y. Takeda, S. Yokotani, T. Nose, Y. Tominaga, M. Shimohigashi, and Y. Shimohigashi, cDNA cloning of the housefly pigment-dispersing factor (PDF) precursor protein and its peptide comparison among the insect circadian neuropeptides, J. Peptide Sci., 10.1002/psc.511, 10, 2, 82-91, 10, 82-91, 2004.01. |
| 121. |
A. Matsushima, S. Yokotani, Y. Shimohigashi, Y. Tominaga, M. Shimohibashi, cDNA Cloning and in situ hybridization studies of sulfated peptide, sulfakinin, on housefly Musca domestica, Peptide Science 2003, 459-462, 2004.01. |
| 122. |
T. Honda, Y. Chuman, A. Matsushima, Y. Nose, K. Sakaguti, H. Onoue, Y. Tominaga, Y. Shimohigashi, and M. Shimohigashi, Localization Profiles of circadian Neuropeptide PDF in Brain of the Cricket Gryllus bimaculatus, Peptide Science 2003, 81-84, 2004.01. |
| 123. |
Y. Takeda, N. Shirasu, S. Sato, A. Matsushima, Y. Chuman, M. Shimohigashi, and Y. Shimohigashi, Two Distinctly Different Isoforms with/without Pentapeptide Fragment in the Silk Moth Clock protein peptide, Peptide Science 2003, 473-476, 2004.01. |
| 124. |
S. Yokotani, A. Matsushima, T. Nose, Y. Shimohigashi, F. Morishita, Effect of the Phe-Phenyl H→F subsutitution in the Sea Hare Aplysia Neuropeptide H-Asn-d-Phe-NH2 on the Conformation and Contraction Activity, Peptide Science 2003, 459-462, 2004.01. |
| 125. |
31. M. Kawano, Y. Horiuchi, T Honda, S. Yokotani, A. Matushima, T, Nose, and Y. Shimohigashi, A. Kaneki, A. Matsushima, Y. Takeda, S. Yokotani, M. Ozaki, M. Shimohigashi, and Y. Shimohigashi, Peptide Science 2003, 483-486, 2004.01. |
| 126. |
31. M. Kawano, Y. Horiuchi, T Honda, S. Yokotani, A. Matushima, T, Nose, and Y. Shimohigashi, Structural Requirements of the N-terminal Octapeptide Repeat of Prion Protein, Peptide Science 2003, 375-378, 2004.01. |
| 127. |
A. Matsushima, T. Nose, Y. Tomioka, M. Shimohigashi, Y. Shimohigashi, Structural characterization of the house fly PDF, a circadian rhythm pacemaker hormone, Peptide Science 2002, 333-336, 2003.01. |
| 128. |
T. Honda, Y. Chuman, A. Matsushima, D. Asai, T. Nose, K. Sakaguchi, H. Onoue, Y. Tominaga, Y. Shimohigashi, and M. Shimohigashi, Localization Profiles of the Precursor Protein of Circadian Rhythm Pacemaker Hormone PDF in Gryllus Brain, Peptide Science 2002, 433-436, 2003.01. |
| 129. |
T. Tokunaga, M. Ohtani, A. Matsushima, T. Nose, M. Shimohigashi, S. Aimoto, and Y. Shimohigashi, The Structure-activity Studies of Drosophila FMRFamide-related Peptides, Peptide Science 2002, 265-268, 2003.01. |
| 130. |
S. Sato, H. Oka, A. Matsushima, Y. Tominaga, Y. Shimohigashi, and M. Shimohigashi, Structural Analysis of PERIOD-PAS Domain Binding Regions in Insect Clock Protein TIMELESS, Peptide Science 2002, 429-432, 2003.01. |
| 131. |
Soto, S., Chuman, Y., Matsushima, A., Tominaga, K., Shimohigashi, Y., and Shimohigashi, M., A Circadian Neuropeptide, Pigment-Dispersing Factor-PDF, in the Last-Summer Cicada Meimuna opalifera: cDNA Cloning and Immunocytochemistry, Zool. Sci., 10.2108/zsj.19.821, 19, 8, 821-828, 19, 821-828, 2002.12. |
| 132. |
Chuman, Y., Matsushima, A., Sato, S., Tomioka, K., Tominaga, Y., Meinertzhagen, I.A., Shimohigashi, Y., and Shimohigashi, M., cDNA Cloning and Nuclear Localization of the Circadian Neuropeptide Designated as Pigment-Dispersing Factor PDF in the Cricket Gryllus bimaculatus, J., Biochem., 131, 6, 895-903, 131, 895-903, 2002.11. |
| 133. |
Matsushima, A., Chuman, Y., Sato, S., Tominaga, Y., Shimohigashi, Y., and Shimohigashi M., Structure and Function of Nuclear Localization Signal Peptide Present in Circadian Rhythm Hormone Peptide Precursor, Comp. Biochem. Physiol., 127, 374, 2002.03. |
| 134. |
Sato, S., Matsushima, A., Chuman, Y., Tominaga, K., Shimohigashi, Y., and Shimohigashi, M., cDNA Cloning of PDF Peptide Precursors in Housefly and Last Summer Cicada, Peptide Science 2001, 139-142, 2002.03. |
| 135. |
Tokunaga, T., Ohtani, M., Matsushima, A., Chuman, Y., Nose, T., Shimohigashi, Y., Aimoto, S., and Shimohigashi, Y., Contractile Activity of Drosophila FMRFamide-Related Peptides in the Meretrix Lusoria Heart Muscle, Peptide Science 2001, 167-170 , 2002.03. |
| 136. |
Asai, D., Tokunaga, T., Matsushima, A., Sato, S., Chuman, Y., Nose, T., Tominaga, Y., Shimohigashi, Y., and Shiimohigashi, M., Design and Preparation of Universal Anti-PERIOD Antibodies and their Immunoresponses, Peptide Science 2001, 399-402, 2002.03. |
| 137. |
Chuman, Y., Matsushima, A., Shimohigashi, Y., and Shimohigashi M., Circadian Rhythm Pacemaker Neuropeptide 'PDF' in Nocturnal Insect Cricket Gryllus bimaculatus: cDNA Cloning, mRNA Expression, and Nuclear Localization, American Peptide Society 2001, 797-798, 2001.03. |
| 138. |
Matsushima, A., Chuman, Y., Onoue, H., Ito, Y., Tomioka, K., Tominaga, Y., Shimohigashi, Y., and Shimohigashi M., Gene Expression of a Circadian Pacemaker Hormone Peptide PDF in Cricket Gryllus bimaculatus,, Peptide Science 2000, 63-66, 2001.03. |
| 139. |
Chuman, A., Matsushima, T., Nose, Y., Shimohigashi, and M., Shimohigashi, cDNA Cloning of Circadian Rhythm Pacemaker Neuropeptide PDF in Gryllus bimaculatus and Its Neuclear Localization, Peptide Science 2000, 59-62, 2001.03. |
| 140. |
Fujita, T., Inoue, N., Matsuhima, A., Nose, T., Costa, T., and Shimohigashi, Y., Activity Enhancement by Introduction of Two Different Halogen Atoms into Phe-2-phenyl Group of Thrombin Receptor Tetherd-Ligand Analogs, Peptide Science 2000, 135-138, 2001.03. |
| 141. |
Matsushima, A., Cuman, Y., Sato, S., Shimohigashi, Y., Tominaga, Y., and Shimohigashi, M., cDNA cloning of a Circadian Rhythm Pacemaker Hormone PDF of theHouse Fly Musca domestica, Comp. Biochem. Physiol., 130, 876, 2001.02. |
| 142. |
Sato, S., Chuman, Y., Matsushima, A., Shimohigashi, Y., Tominaga, Y., and Shimohigashi, M., PERIOD Clock Protein of the Summer Cicada Meimuna opalifera: cDNA Cloning and Structural Analysis, Comp. Biochem. Physiol., 130, 874, 2001.02. |
| 143. |
Fujita, T., Nose, T., Matsushima, A., Costa, T., and Shimohigashi, Y., Highly Potent Peptide Ligands for Thrombin Receptor, Peptide Science 1999, 421-424, 2000.03. |
| 144. |
Matsushima, A., Fujita, T., Okada, K., Yamauchi, Y., Nose, T., and Shimohigashi, Y., Chemical Syntheses of Phenylalanine Derivatives Containing Halogenated Benzene Ring as Structural Explorers for Elucidation of Molecular Mechanisms of Receptor Interactions, Peptide Science 1999, 141-142, 2000.03. |
| 145. |
Matsushima, A., Fujita, T., Okada, K., Shirasu, N., Nose, T., and Shimohigashi, Y., Exploration of the Role of Phenylalanine in the Thrombin Rwcwptor Tethered-Ligand Peptide by Substitution with a Series of Trifluorophenylalanines, Bull. Chem. Soc. Jpn, 10.1246/bcsj.73.2531, 73, 11, 2531-2538, 73, 2531-2538 , 2000.02. |
| 146. |
Matsushima, A., Fujita, T., Okada, K., Nose, T., and Shimohigashi, Y., Edge-to-face CH/π Interaction between Ligand Phe-phenyl and Receptor Aromatic Group in Thrombin Receptor Activation, J. Biochem., 128, 2, 225-232, 128, 225-232, 2000.02. |
| 147. |
Fujita, T., Nose, T., Matsushima, A., Okada, K., Asai, D., Yamauchi, Y., Shirasu, N., Honda, T., Shigehiro, D., and Shimohigashi, Y., Synthesis of complete set of L-difluorophenylalanines, L-(F2)Phe, as molecular explorers for the CH/π interaction between peptide ligand and receptor , Tetrahedron Letters, 41, 923-927 , 2000.02. |
| 148. |
Fujita,T., Nose, T., Matsushima, A., Costa, T., and Shimohigashi, Y., Importance of Ligand Phe-phenyl Group for Activation of Thrombin Receptor, Peptide Science 1998, 33-36, 1999.03. |
