Establishment of the molecualr basis underlying regulation of cardiac redox homeostasis by electrophilic signaling and its therapeutic application for heart failure

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670031
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Okazaki Research Facilities, National Institutes of Natural Sciences
• Principal Investigator: NISHIDA Motohiro 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (90342641)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 活性酸素 / 硫黄 / 循環 / 心不全

Outline of Final Research Achievements

We have reported the possibility that hydrogen sulfide anion (H2S/HS-) protects against chronic heart failure via nucleophilic elimination of endogenous electrophiles in mouse hearts after myocardial infarction. However, it is still obscure whether H2S/HS- acts as a molecular entity of reactive nucleophile in hearts. In this study, we aim to identify the molecular entity of nucleophilic reactive sulfur species (RSS) in hearts and establish an innovative strategy based on the to treat chronic heart failure. We found that proteins containing cysteine persulfide or polysulfide acts as RSS, and accumulation of RSS by taking a polysulfur (garlic)-containing diet dramatically suppresses cardiac risk after myocardial infarction in mice. These results strongly suggest that preservation of RSS in heart will be a novel strategy to reduce cardiac risk.

Free Research Field

薬理学