核内受容体の作用発現機構解析と化学物質リスク評価に関する研究
キーワード:コンホメーション変化、核内受容体、ビスフェノールA、転写、内分泌撹乱、化学物質リスク
2005.04.
松島 綾美(まつしま あやみ) | データ更新日:2023.12.06 |
主な研究テーマ
痛み増強ノシセプチン受容体をブロックする純アンタゴニスト鎮痛薬の開発
キーワード:鎮痛、疼痛、ノシセプチン受容体、創薬、
2010.04.
キーワード:鎮痛、疼痛、ノシセプチン受容体、創薬、
2010.04.
プリオンタンパク質のコンホメーション変化誘導の構造要因解析に関する研究
キーワード:コンホメーション変化、プリオン、分子間相互作用
2004.04.
キーワード:コンホメーション変化、プリオン、分子間相互作用
2004.04.
新規概日時計関連ペプチドの同定と構造機能解析に関する研究
キーワード:受容体、概日リズム
2001.04.
キーワード:受容体、概日リズム
2001.04.
含フッ素フェニルアラニンを用いたトロンビン受容体の構造活性相関に関する研究
キーワード:受容体、構造活性相関、分子間相互作用
1999.04.
キーワード:受容体、構造活性相関、分子間相互作用
1999.04.
研究業績
主要原著論文
1. | 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, [URL], 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.. |
2. | 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, [URL], 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.. |
3. | 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, [URL], 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.. |
4. | 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, [URL], 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.. |
5. | 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, [URL], 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.. |
6. | 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. |
7. | 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. |
8. | 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. |
9. | 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. |
10. | 劉 暁輝, 松島 綾美, 下東 康幸, 乳がん細胞におけるビスフェノールのエストロゲン様活性, BIO Clinica(北隆館), 30, 10, 90-95, 2015.10. |
11. | 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. |
12. | 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. |
13. | 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. |
14. | 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. |
15. | 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.. |
16. | 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. |
17. | 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.. |
18. | 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.. |
19. | 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. |
20. | 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. |
21. | 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. |
22. | 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. |
23. | 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. |
24. | 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. |
25. | 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. |
26. | 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. |
27. | 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. |
28. | 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. |
29. | 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. |
30. | 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. |
31. | 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. |
32. | 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. |
33. | 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. |
34. | 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. |
35. | 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. |
36. | 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. |
37. | 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. |
38. | 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. |
39. | 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. |
40. | 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. |
41. | 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. |
42. | 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. |
43. | 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. |
44. | 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. |
45. | 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. |
46. | 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. |
47. | 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. |
48. | 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. |
49. | 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. |
50. | 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. |
51. | 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. |
52. | 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. |
53. | 松島綾美、下東康幸、下東美樹, 昆虫の概日リズムペースメーカーペプチドホルモンPDF, 比較生理生化学, 18(3), 159-166, 2002.02. |
54. | 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. |
55. | 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. |
56. | 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. |
57. | 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. |
58. | 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. |
59. | 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. |
60. | 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. |
61. | 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. |
62. | 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. |
63. | 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. |
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
学会活動
学協会役員等への就任
2023.06~2025.06, 環境ホルモン学会, 理事.
2017.11~2022.10, DV-Xa研究会, 幹事.
2018.06~2025.06, 環境ホルモン学会, 評議員.
2018.04~2022.03, 日本ペプチド学会, 評議員.
2016.09~2017.11, 日本生化学会, 代議員.
2014.11~2022.10, 日本生化学会(九州支部), 評議員.
2015.10~2018.09, 日本生化学会, 男女共同参画委員.
2015.06~2017.05, 日本生化学会, 男女共同参画推進委員.
2013.11~2014.10, 日本化学会九州支部, 日本化学会九州支部平成26年度代議員.
2014.03~2015.02, 日本化学会九州支部, 幹事.
学会大会・会議・シンポジウム等における役割
2023.05.29~2023.06.02, 環境化学物質3学会合同大会, 座長.
2016.10.26~2016.10.28, 第53回ペプチド討論会, 座長(Chairmanship).
2016.05.21~2016.05.22, 平成28年度日本生化学会九州支部例会, 座長(Chairmanship).
2015.11.06~2015.11.07, 第52回ペプチド討論会, 座長(Chairmanship).
2015.05.16~2015.05.17, 平成27年度日本生化学会九州支部例会, 座長(Chairmanship).
2015.03.09~2015.03.09, リスクサイエンス研究フォーラム2014, 座長(Chairmanship).
2014.10.22~2014.10.24, 第51回ペプチド討論会, 座長(Chairmanship).
2014.03.10~2014.03.10, リスクサイエンス研究フォーラム2014「化学物質の受容体シグナル毒性ー多様な挑戦的解析研究」, 会計.
2014.02.17~2014.02.17, 第2回Organelle Homeostasis Research Center 研究発表会 , 座長(Chairmanship).
2013.05.18~2013.05.19, 平成25年度日本生化学会九州支部例会, 座長(Chairmanship).
2012.11.07~2012.11.09, 第49回ペプチド討論会, 座長(Chairmanship).
2012.05.26~2012.05.27, 平成24年度日本生化学会九州支部例会, 座長(Chairmanship).
2011.05.21~2011.05.22, 平成23年度日本生化学会九州支部例会, 座長(Chairmanship).
2010.07.17~2010.07.19, 比較生理生化学会 第32回大会, 実行委員.
2010.05.22~2010.05.23, 平成22年度日本生化学会九州支部例会, 座長(Chairmanship).
2009.11.04~2009.11.06, 第46回ペプチド討論会, 実行委員.
2009.05.16~2009.05.17, 平成21年度日本生化学会九州支部例会, 座長(Chairmanship).
2007.11, 第44回ペプチド討論会, 座長(Chairmanship).
2006.05~2007.04, 平成18年度日本生化学会九州支部例会, 実行委員.
2004.10~2005.09, 第1回アジア太平洋国際ペプチドシンポジウム, 実行委員.
学会誌・雑誌・著書の編集への参加状況
2017.12~2019.12, 日本ペプチド学会HP, 国内, 編集委員.
2008.04~2017.12, 日本ペプチド学会ペプチドニュースレター, 国内, 編集委員.
学術論文等の審査
年度 | 外国語雑誌査読論文数 | 日本語雑誌査読論文数 | 国際会議録査読論文数 | 国内会議録査読論文数 | 合計 |
---|---|---|---|---|---|
2020年度 | 7 | 2 | 9 | ||
2019年度 | 4 | 2 | 6 | ||
2018年度 | 4 | 2 | 6 | ||
2017年度 | 6 | 2 | 8 | ||
2016年度 | 1 | 2 | 3 | ||
2015年度 | 3 | 2 | 5 | ||
2014年度 | 2 | 0 |
その他の研究活動
海外渡航状況, 海外での教育研究歴
Salk研究所, UnitedStatesofAmerica, 2019.06~2020.02.
Dalhousie大学, Canada, 2009.07~2010.01.
受賞
平成28年度科研費審査委員表彰における表彰者, 日本学術振興会, 2016.09.
平成27年度日本化学会女性化学者奨励賞, 日本化学会, 2016.03.
平成27年度日本生化学会学術奨励賞, 日本生化学会, 2015.12.
平成23年度日本生化学会九州支部学術奨励賞, 日本生化学会九州支部, 2011.05.
公益財団法人国際科学技術財団研究助成, 公益財団法人国際科学技術財団, 2011.12.
平成23年度科学技術分野の文部科学大臣表彰 若手科学者賞, 文部科学省, 2011.04.
Best Poster 賞, 万有生命科学振興国際交流財団第14回福岡シンポジウム, 2004.05.
The 5th Australian Peptide Conference Student Bursaries, The 5th Australian Peptide Conference, 2003.10.
The 1st World Congress of Chronobiology 2003 Travel Grant, The 1st World Congress of Chronobiology 2003, 2003.09.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2023年度~2026年度, 基盤研究(A), 代表, 核内受容体とリピート病から紐解く環境化学物質による胎児期脳神経系影響の発現基盤.
2020年度~2023年度, 基盤研究(A), 代表, 新世代ビスフェノール胎児期暴露とスーパーエンハンサーから探る低用量効果の分子基盤.
2019年度~2021年度, 国際共同研究強化(A), 代表, 新世代ビスフェノールによる新規な肥満誘導メカニズムの解明.
2018年度~2020年度, 挑戦的研究(萌芽), 代表, ドパミンニューロン分化誘導核内受容体Nurr1の制御によるパーキンソン病薬の創製.
2017年度~2019年度, 基盤研究(B), 代表, 新世代ビスフェノールのシグナル毒性を増強する核内受容体協働作用機構の解明.
2014年度~2015年度, 挑戦的萌芽研究, 代表, ゲノムに潜む鎮痛ペプチド・エンドモルフィンは酸化ストレスのRNA編集で誕生する.
2013年度~2016年度, 若手研究(A), 代表, ビスフェノール低用量効果はタンデムに並ぶ核内受容体が誘起する.
2010年度~2012年度, 基盤研究(C), 代表, 痛み増強ノシセプチン受容体をブロックする純アンタゴニスト鎮痛薬の開発.
2008年度~2009年度, 若手研究(B), 代表, ERRγへテロダイマー受容体を介したビスフェノールAのエストロゲン様低用量活性.
2004年度~2004年度, 特別研究員奨励費, 代表, プリオンタンパク質のコンホメーション変化誘導の構図要因と誘導要因センシング.
2001年度~2003年度, 特別研究員奨励費, 代表, 概日リズムの新規ペースメーカーホルモンの同定と構造機能解析.
競争的資金(受託研究を含む)の採択状況
2012年度~2012年度, 公益財団法人 国際科学技術財団「2012年研究助成」, 代表, 胎児および乳幼児の脳神経系に悪影響を与える有害環境化学物質ビスフェノールAの低用量作用発現機構の解明.
2012年度~2013年度, 第24回(平成24年度)加藤記念研究助成, 代表, パーキンソン病誘因ドーパミンニューロンの分化誘導核内受容体Nurr1の自発活性制御低分子化合物の探索.
2006年度~2006年度, 財団法人持田記念医学薬学振興財団研究助成, 代表, ORL1受容体の活性化/不活性化機構解明に基づく純アンタゴニスト設計.
寄附金の受入状況
2020年度, 泉科学振興財団研究助成.
2018年度, 公益財団法人豊田理化学研究所, トヨタ理研スカラー研究助成:共同:「分子間相互作用を利用したフィルター型分離リアクターの開発」.
2017年度, 公益財団法人豊田理化学研究所, トヨタ理研スカラー研究助成「新規な薬剤結合増強法を目指したエストロゲン関連受容体とハロゲン化フェノールの結合解析」.
2017年度, 第28回(平成28年度)加藤記念研究助成(2017−2018年度).
2014年度, 第24回(平成24年度)加藤記念研究助成(2013−2014年度).
学内資金・基金等への採択状況
2016年度~2016年度, QRプログラム(Qdai-jump Research Program), 代表, ビスフェノールA低用量作用の分子機構解明を目指した核内受容体協働効果の解析.
2014年度~2014年度, 最先端研究基盤事業「化合物ライブラリーを活用した創薬等最先端研究・教育基盤の整備」のコンペ, 代表, パーキンソン病改善に繋がるドパミン生成必須酵素の転写因子Nurr1の活性制御低分子探索(継続課題).
2012年度~2012年度, 最先端研究基盤事業「化合物ライブラリーを活用した創薬等最先端研究・教育基盤の整備」のコンペ, 代表, パーキンソン病改善に繋がるドパミン生成必須酵素の転写因子Nurr1の活性制御低分子探索.
2007年度~2008年度, 九州大学教育研究プログラム研究拠点形成プロジェクト(P&P), 代表, 環境ホルモン・ビスフェノールA受容体の作用発現機構解析と新リスク評価法の確立.
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QIR 九州大学学術情報リポジトリ システム情報科学研究院
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