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Neuronal Death and Neuroprotection

開催日 2014/9/11
時間 17:00 - 18:00
会場 Room I(311+312)
Chairperson(s) 木村 英雄 / Hideo Kimura ((独)国立精神・神経医療研究センター 神経研究所 神経薬理研究部 / Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Japan)
小笠原 裕樹 / Yuki Ogasawara (明治薬科大学 分析化学教室 / Department of Analytical Biochemistry, Meiji Pharmaceutical University, Japan)

A Novel Pathway for the Production of Hydrogen Sulfide from D-Cysteine in Mammalian Cells

  • O1-I-5-2
  • 渋谷 典広 / Norihiro Shibuya:1 小池 伸 / Shin Koike:2 田中 真紀子 / Makiko Tanaka:1 湯浅(石上) 磨里 / Mari Ishigami-Yuasa:1 木村 由佳 / Yuka Kimura:1 小笠原 裕樹 / Yuki Ogasawara:2 福井 清 / Kiyoshi Fukui:3 永原 則之 / Noriyuki Nagahara:4 木村 英雄 / Hideo Kimura:1 
  • 1:国立精神・神経セ神経研神経薬理 / Dept Mol Pharm, Natl Inst Neurosci, NCNP, Tokyo, Japan 2:明治薬大・分析化学 / Dept Anal Chem, Meiji Pharm Univ, Tokyo, Japan 3:徳島大・疾患酵素学研究セ / Inst Enzyme Res, Univ of Tokushima, Tokushima, Japan 4:日本医科大・アイソトープセ / Isotope Res Center, Nippon Med Sch, Tokyo, Japan 

In eukaryotes, hydrogen sulfide (H2S) acts as a signaling molecule and cytoprotectant. It modulates synaptic transmission, relaxes smooth muscle, and regulates a release of insulin, endoplasmic reticulum stress and apoptosis. H2S also protects neurons and cardiac muscle from oxidative stress and ischemia reperfusion injury. H2S is known to be produced from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) coupled with cysteine aminotransferase (CAT). Here we report an additional biosynthetic pathway for the production of H2S from D-cysteine involving 3MST and D-amino acid oxidase (DAO). Unlike the L-cysteine pathway, this D-cysteine-dependent pathway seems to operate predominantly in the cerebellum and the kidney. Our study revealed that administration of D-cysteine protected primary cultures of cerebellar neurons from oxidative stress induced by H2O2 and attenuated ischemia-reperfusion injury in the kidney more than L-cysteine. This study presents a novel pathway of H2S production and provides a new therapeutic approach to deliver H2S to specific tissues.

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