title: Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.
abstract: An emerging aspect of redox signaling is the pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (for example, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)) and nitro or keto derivatives of unsaturated fatty acids, generated via reactions of inflammation-related enzymes, reactive oxygen species, nitric oxide and secondary products. Here we report that enzymatically generated hydrogen sulfide anion (HS(-)) regulates the metabolism and signaling actions of various electrophiles. HS(-) reacts with electrophiles, best represented by 8-nitro-cGMP, via direct sulfhydration and modulates cellular redox signaling. The relevance of this reaction is reinforced by the significant 8-nitro-cGMP formation in mouse cardiac tissue after myocardial infarction that is modulated by alterations in HS(-) biosynthesis. Cardiac HS(-), in turn, suppresses electrophile-mediated H-Ras activation and cardiac cell senescence, contributing to the beneficial effects of HS(-) on myocardial infarction-associated heart failure. Thus, this study reveals HS(-)-induced electrophile sulfhydration as a unique mechanism for regulating electrophile-mediated redox signaling.
authors: Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Motohiro
authors: M
authors: Nishida
authors: Tomohiro
authors: T
authors: Sawa
authors: Naoyuki
authors: N
authors: Kitajima
authors: Katsuhiko
authors: K
authors: Ono
authors: Hirofumi
authors: H
authors: Inoue
authors: Hideshi
authors: H
authors: Ihara
authors: Hozumi
authors: H
authors: Motohashi
authors: Masayuki
authors: M
authors: Yamamoto
authors: Makoto
authors: M
authors: Suematsu
authors: Hitoshi
authors: H
authors: Kurose
authors: Albert
authors: A
authors: van der Vliet
authors: Bruce A
authors: BA
authors: Freeman
authors: Takahiro
authors: T
authors: Shibata
authors: Koji
authors: K
authors: Uchida
authors: Yoshito
authors: Y
authors: Kumagai
authors: Takaaki
authors: T
authors: Akaike
mesh_terms: D000818:Animals; D000838:Anions; D002460:Cell Line; D002462:Cell Membrane; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000378:metabolism; D010084:Oxidation-Reduction; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C525106:8-nitroguanosine 3',5'-cyclic monophosphate; D000838:Anions; D006152:Cyclic GMP; D006862:Hydrogen Sulfide