Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

• Type of Material: Article
• Authors: Adrienne King, Emory University; David J. Polhemus, Louisiana State University; Shashi Bhushan, Louisiana State University; Hiroyuki Otsuka, Louisiana State University; Kazuhisa Kondo, Emory University; Chad K. Nicholson, Emory University; Jessica M. Bradley, Louisiana State University; Kazi N. Islam, Louisiana State University; John Calvert, Emory University; Ya-Xiong Tao, Auburn University; Tammy R. Dugas, Louisiana State University; Eric E. Kelley, University of Pittsburgh; John W. Elrod, Temple University; Paul L. Huang, Massachusetts General Hospital; Rui Wang, Lakehead University; David J. Lefer, Louisiana State University
• Language: English
• Date: 2014-02-25
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2014 National Academy of Sciences
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1321871111
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 111
• Issue: 8
• Start Page: 3182
• End Page: 3187
• Grant/Funding Information: This work was supported by Grants from the National Heart, Lung, and Blood Institute (1R01 HL092141, 1R01 HL093579, 1U24 HL 094373, and 1P20 HL113452 to D.J.L., and 5R01 HL 098481 to J.W.C.).; We are also grateful for the generous financial support from the Carlyle Fraser Heart Center of Emory University and the Louisiana State University Health Foundation in New Orleans.; These studies were also supported by the Canadian Institutes of Health Research (R.W.).
• Keywords: PROTECTS; myocardial infarction; MOUSE HEART; H2S; MULTIDISCIPLINARY SCIENCES; eNOS uncoupling; cystathionase; Science & Technology; INDUCED HEART-FAILURE; ISCHEMIA-REPERFUSION INJURY; IN-VIVO; Science & Technology - Other Topics; AKT; Cth; nitrite; MYOCARDIAL ISCHEMIA; Multidisciplinary Sciences; PHOSPHORYLATION; CYTOCHROME-C-OXIDASE
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology

Abstract

Previous studies have demonstrated that hydrogen sulfide (H 2 S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H 2 S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H 2 S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H 2 S-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 H 2 S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H 2 S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H 2 S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.