Clarification of the endogenous formation of the novel cyclic nucleotide 8-SH-cGMP and its signaling function

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870549
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology; General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: IDA Tomoaki 東北大学, 医学(系)研究科(研究院), 助教 (70570406)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 8-SH-cGMP / 8-ニトロ-cGMP / 活性イオウ分子種 / S-S-グアニル化 / S-ポリチオール化タンパク質 / タンパク質翻訳後修飾 / 酸化ストレス

Outline of Final Research Achievements

The cyclic nucleotide 8-SH-cGMP is produced by the metabolism of 8-nitro-cGMP, which serves as a secondary messenger for NO and reactive oxygen species signaling. However, the mechanisms controlling the formation and levels of intracellular 8-SH-cGMP have not yet been identified. In this study, the principal investigator precisely quantified the formation of 8-SH-GMP via a mass spectrometry-based metabolomic method. The results revealed that 8-SH-cGMP is produced from 8-nitro-cGMP via sulfhydration by reactive sulfur species generated from the cystathione beta-synthase and cystathionine gamma-lyase systems. Moreover, the formation of S-S-guanylation (cGMP adduction to the thiol group of the protein via disulfide linkage) was specifically identified using proteome analysis of S-polythiolation.

Free Research Field

ケミカルバイオロジー