Regulation of Redox Signaling by a Nitrated Nucleotide and Reactive Cysteine Persulfides

Tomohiro Sawa, Yoshito Kumagai, Takaaki Akaike

研究成果: Chapter

抄録

Nitric oxide (NO) and reactive oxygen species (ROS) cooperatively participate in the regulation of cellular signaling, at least in part, via posttranslational modifications of protein thiols. 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated derivative of guanosine 3',5'-cyclic monophosphate (cGMP) formed endogenously under conditions associated with production of both NO and ROS. It acts as an electrophilic second messenger in regulation of cellular signaling by inducing posttranslational modification of redox-sensitive protein thiols via covalent adduction of cGMP moieties to protein thiols (protein S-guanylation). Site-specific S-guanylation of redox sensor proteins, such as Keap1 (the negative regulator of transcription factor Nrf2), H-Ras (small GTPase), HSP60 (mitochondrial heat shock protein), and cGMP-dependent protein kinase 1 has been implicated in the regulation of diverse cellular functions including antioxidant adaptation, cellular senescence, mitochondrial permeability pore opening, and vascular relaxation. We recently demonstrated that reactive cysteine persulfides are formed abundantly in cells and critically involved in regulation of redox signaling possibly via multiple mechanisms; that is, sulfhydration of electrophiles, reduction of cellular ROS levels, and formation of protein persulfides/polysulfides. In this chapter, we discuss the regulatory mechanisms of redox signaling with particular emphasis on the roles of 8-nitro-cGMP and reactive cysteine persulfides. Environmental electrophiles are an alternative important species involved in redox signaling, and we will discuss their metabolic regulation by reactive cysteine persulfides.

本文言語English
ホスト出版物のタイトルNitric Oxide
ホスト出版物のサブタイトルBiology and Pathobiology: Third Edition
出版社Elsevier Inc.
ページ231-235
ページ数5
ISBN(印刷版)9780128042731
DOI
出版ステータスPublished - 2017 1 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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