私たちは常に食品や環境中から種々の化学物質を取り込んでいるが、その有害な作用発現を防ぐには、どのようにして化学物質の毒性が発現するのかを理解する必要がある。化学物質が体内で変化して毒性を現すまでの過程と、それらの物質がタンパク質や核酸などの標的とどのように相互作用するのかについて研究を進めている。

1. 重金属応答性転写因子を介した生体防御機構の解析
2. ヌクレオチド3'-AMP産生に関与する酵素系とその生理機能
3. 新規糖尿病治療薬および免疫抑制剤の細胞内情報伝達系に及ぼす影響
4. 重金属汚染土壌を浄化する植物の分子育種

• 磯部 正和　isobe＠pharm.setsunan.ac.jp
• 藤森 廣幸　fujihiro＠pharm.setsunan.ac.jp
• 木村 朋紀　tomoki＠pharm.setsunan.ac.jp
• 宮本 晃洋　miyamoto＠pharm.setsunan.ac.jp
• 保坂 卓臣　hosaka＠pharm.setsunan.ac.jp

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2. Yamamuro A, Kishino T, Ohshima Y, Yoshioka Y, Kimura T, Kasai A, Maeda S. (2011) Caspase-4 Directly Activates Caspase-9 in Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells. J Pharmacol Sci, 115(2), 239-43
3. Okumura, F., Li,Y., Itoh, N., Nakanishi, T., Isobe, M., Andrews, G.K., Kimura, T. (2011) The zinc-sensing transcription factor MTF-1 mediates zinc-induced epigenetic changes in chromatin of the mouse metallothionein-I promoter. Biochim Biophys Acta - Gene Regulatory Mechanisms, 1809(1), 56-62
4. Kimura, T., (2010) Molecular mechanisms of zinc-mediated induction and chromium(VI)-mediated inhibition of mouse metallothionein-I gene transcription. J Health Sci, 56(2), 161-166
5. Kimura, T., Itoh, N., and Andrews, G.K. (2009) Mechanisms of heavy metal sensing by metal response element-binding transcription factor-1 J Health Sci, 55(4), 484-494
6. Kimura, T., Kawasaki, Y., Okumura, F., Sone, T., Natsuki, R., and Isobe, M. (2009) Ethanol-induced expression of glutamate-cysteine ligase catalytic subunit gene is mediated by NF-kappaB. Toxicol Lett, 185(2), 110-115
7. Kimura, T., Okumura, F., Oguro, I., Nakanishi, T., Sone, T., Isobe, M., Tanaka, K., and Itoh, N. (2009) Metal response element-binding transcription factor-1 is activated by degradation of metallothionein. J Health Sci, 55(1), 72-76
8. Kimura, T., Li, Y., Okumura, F., Itoh, N., Nakanishi, T., Sone, T., Isobe, M., and Andrews, G.K. (2008) Chromium (VI) inhibits mouse metallothionein-I gene transcription by preventing the zinc-dependent formation of an MTF-1--p300 complex. Biochem J, 415(3), 477-482
9. Li, Y., Kimura, T., Huyck, R.W., Laity, J.H., and Andrews, G.K. (2008) Zinc-induced formation of a co-activator complex containing the zinc-sensing transcription factor MTF-1, p300/CBP and Sp1. Mol Cell Biol, 28(13), 4275-4284
10. Nagata, T., Kimura, T., and Pan-Hou, H. (2008) Engineering expression of polyphosphate confers cadmium resistance in tabacco. J Toxicol Sci, 33(3), 371-373
11. Miyamoto, A., Takeshita, M., Pan-Hou, H., and Fujimori, H. (2008) Hepatic changes in adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in streptozotocin-induced diabetic mice. J Toxicol Sci. 33(2), 209-217
12. Kimura, T., and Itoh, N. (2008) Function of metallothionein in gene expression and signal transduction - Newly found protective role of metallothionein. J Health Sci 54(3), 251-260
13. Murphy, B.J., Kimura, T., Sato B.G., Shi, Y., and Andrews, G.K. (2008) Metallothionein induction by hypoxia involves cooperative interactions between MTF-1 and HIF-1alpha. Mol Cancer Res 6, 483-490
14. 木村朋紀 (2007) 亜鉛応答性転写因子MTF-1とCr(VI)毒性−6価クロムの発がん性と遺伝子発現抑制作用との関係− Molecular Mechanism involved in chromium (VI) toxicity. 薬学雑誌、127(12):1957-1965
15. Nakamura, Y., Sugihara, K., Sone, T., Isobe, M., Ohta, S., and Kitamura, S.. (2007) The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats. Toxicology 235, 176-184
16. 伊藤徳夫、木村朋紀 (2007)サイトカインによるメタロチオネイン誘導とメタロチオネインによるサイトカイン発現の修飾 Cytokine-induced Metallothionein Expression and Modulation of Cytokine Expression by Metallothionein. 薬学雑誌、127(4):685-694