Functional relationship between metabolism of sulfur-containing amino acids and cardioprotection from ischemia-reperfusion injury

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Keio University
• Principal Investigator: Ishii Isao 慶應義塾大学, 薬学部, 准教授 (90292953)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ホモシステイン / 硫化水素 / 心血管病 / 危険因子 / 活性イオウ分子 / 虚血再灌流障害 / 硫黄転移経路 / システイン

Outline of Final Research Achievements

Elevated levels of homocysteine in plasma are considered as a risk factor for cardiovascular diseases; however, how homocysteine works are still largely unclear. We aim to reveal its molecular mechanisms through investigating genetically engineered mice lacking CBS and CTH, two trans-sulfuration enzymes essential for cysteine biosynthesis from homocysteine as well as for endogenous production of bioactive (cell-protective) hydrogen sulfide production. In this project, we obtained experimental evidence as a novel mechanism of homocysteine actions that homocysteine directly captures a hydrogen sulfide anion (by forming homocysteine persulfide), thereby counteracting their biological effects. Our results suggest that the regulation of hydrogen sulfide signaling may contribute to the amelioration of homocysteine-related cardiovascular diseases.

Free Research Field

生化学・病態生理学