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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)

The regulation of H2S production and its role in the retina

  • O1-I-5-1
  • 木村 英雄 / Hideo Kimura:1 三上 義礼 / Yoshinori Mikami:1,5 渋谷 典広 / Norihiro Shibuya :1 木村 由佳 / Yuka Kimura:1 小笠原 裕樹 / Yuki Ogasawara:2 永原 則之 / Noriyuki Nagahara:3 山田 雅弘 / Masahiro Yamada:4 
  • 1:国立精神・神経医療研究センター神経研究所 / Nat'l Inst.of Neurosci., NCNP, Japan 2:明治薬大 / Meiji Pharm. Univ. Tokyo, Japan 3:日本医大 / Nippon Medical School, Tokyo, Japan 4:埼玉医大 / Saitama Medical School, Saitama, Japan 5:東大 / Tokyo Univ. Tokyo, Japan 

Hydrogen sulfide (H2S) is a signaling molecule in various tissues and organs. We demonstrated H2S as a neuromodulator in the brain with its producing enzyme cystathionine beta-synthase (CBS) in 1996. In the following year, we demonstrated H2S as a vascular smooth muscle relaxant in synergy with nitric oxide (NO) with cystathionine gamma-lyase (CSE) as another producing enzyme. We also found the cytoprotective effect of H2S; H2S protects neurons from oxidative stress. In addition to CBS and CSE we found 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) produces H2S in the brain, retina and vascular endothelium. Although 3MST requires a reducing substance to produce H2S, the endogenous reducing substance has not been identified. We found that thioredoxin and dihydrolipoic acid (DHLA) are the endogenous reducing substances to make 3MST produce H2S. H2S production by 3MST is also regulated by Ca2+; the production is maximal in the absence of Ca2+ and is suppressed by Ca2+ in a concentration-dependent manner. Calmodulin is not involved in this regulation by Ca2+. In the retina H2S suppresses Ca2+ influx and maintains the intracellular Ca2+ concentrations at low levels. H2S protects retinal neurons from light-induced degeneration.

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