Study on a second messenger, 8-mercapt-cGMP, of hydrogen sulfide in nervous system

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka Prefecture University
• Principal Investigator: Ihara Hideshi 大阪府立大学, 理学(系)研究科(研究院), 准教授 (60254447)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 8-メルカプト-cGMP / 8-ニトロ-cGMP / システインパーサルファイド / 活性イオウ分子 / メチル水銀 / レドックスシグナル

Outline of Final Research Achievements

It is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. Quantitation of these species indicates that high　concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the　plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing.　This view was found to be the case, because they quickly react with　H2O2 and a recently described biologically generated electrophile 8-nitro-cGMP to form 8-mercapt-cGMP. Indeed, 8-mercapt-cGMP formation in nervous system was confirmed by LC-MSMS and immunocytochemistry. Furthermore, a novel mechanism of methylmercury-induced cytotoxicity, that is disruption of redox signaling regulated reactive sulfur species, was also revealed.

Free Research Field

神経化学