title: Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent.
abstract: Previous studies have demonstrated that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H2S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H2S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H2S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H2S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.
authors: Department of Surgery and Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA 30308.
authors: Adrienne L
authors: AL
authors: King
authors: David J
authors: DJ
authors: Polhemus
authors: Shashi
authors: S
authors: Bhushan
authors: Hiroyuki
authors: H
authors: Otsuka
authors: Kazuhisa
authors: K
authors: Kondo
authors: Chad K
authors: CK
authors: Nicholson
authors: Jessica M
authors: JM
authors: Bradley
authors: Kazi N
authors: KN
authors: Islam
authors: John W
authors: JW
authors: Calvert
authors: Ya-Xiong
authors: YX
authors: Tao
authors: Tammy R
authors: TR
authors: Dugas
authors: Eric E
authors: EE
authors: Kelley
authors: John W
authors: JW
authors: Elrod
authors: Paul L
authors: PL
authors: Huang
authors: Rui
authors: R
authors: Wang
authors: David J
authors: DJ
authors: Lefer
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003542:Cystathionine gamma-Lyase / Q000235:genetics; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019210:Troponin I / Q000378:metabolism
chemical_list: D019210:Troponin I; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: Cth; cystathionase; eNOS uncoupling; myocardial infarction; nitrite