Analysis of a novel pathway to produce hydrogen sulfide

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15123
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Shibuya Norihiro 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 神経薬理研究部, 流動研究員 (40466214)
• Research Collaborator: Kimura Hideo ; Ogasawara Yuki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 硫化水素 / D-システイン / 3MST / 虚血再灌流障害

Outline of Final Research Achievements

Hydrogen sulfide (H2S) modulates synaptic activity in the brain and relaxes vasculature. In addition to its function as a signaling molecule, H2S has a cytoprotective effect. H2S is produced from L-cysteine by three different H2S-produsing enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT). An additional pathway for the production of H2S is from D-cysteine by 3MST and D-amino acid oxidase (DAO). We found that N-acetyl-D-cysteine attenuates ischaemia-reperfusion injury caused in the kidney more effectively than D-cysteine. We also found that 3MST protein levels decreased at early-time points after the renal insult, but not CSE and CBS levels, suggesting that 3MST is susceptible to ischaemia-reperfusion injury. This study presents a new therapeutic approach to deliver H2S to the kidney and provides novel approach to examine the mechanisms of ischaemia-reperfusion injury.

Free Research Field

薬理学、生化学

Academic Significance and Societal Importance of the Research Achievements

腎障害は生命を脅かす危険性があり、治療には透析療法を導入することが少なくない。しかしながら、一旦導入すると長期間の透析を強いられるなどの負担が大きい。これに対して本研究では、D‐システインもしくはN‐アセチル‐D‐システインを腎不全の予防や重篤化の防止に役立てることができる可能性を示した。
虚血再還流障害の軽減機構を解明するためには、再灌流障害の発生初期段階におけるH2S産生酵素群の量的変化の観点から解析を進める必要性があると考えられる。本研究によって、H2S産生酵素群の時系列変化という新たな視点から腎虚血再還流障害の発症、進展、あるいは軽減機構を解明できると考えられる。