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

نویسندگان

  • Adrienne L King
  • David J Polhemus
  • Shashi Bhushan
  • Hiroyuki Otsuka
  • Kazuhisa Kondo
  • Chad K Nicholson
  • Jessica M Bradley
  • Kazi N Islam
  • John W Calvert
  • Ya-Xiong Tao
  • Tammy R Dugas
  • Eric E Kelley
  • John W Elrod
  • Paul L Huang
  • Rui Wang
  • David J Lefer
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 111 8  شماره 

صفحات  -

تاریخ انتشار 2014