Postconditioning leads to an increase in protein S-nitrosylation

Guang Tong, Angel M. Aponte, Mark Kohr, Charles Jr Steenbergen, Elizabeth Murphy, Junhui Sun

Research output: Contribution to journalArticle

Abstract

Previous studies have shown a role for nitric oxide and S-nitrosylation (SNO) in postconditioning (PostC), but specific SNO proteins and sites have not been identified in the myocardium after PostC. In this study, we examined SNO signaling in PostC using a Langendorff-perfused mouse heart model. After 20 min of equilibrium perfusion and 25 min of global ischemia, PostC was applied at the beginning of reperfusion with six cycles of 10 s of reperfusion and 10 s of ischemia. The total period of reperfusion was 90 min. Compared with the ischemia-reperfusion (I/R) control, PostC significantly reduced postischemic contractile dysfunction and infarct size. PostC-induced protection was blocked by treatment with NG-nitro-L-arginine methyl ester (L-NAME) (10 μmol/l; a constitutive NO synthase inhibitor), but not by either ODQ (10 μmol/l, a highly selective soluble guanylyl cyclase inhibitor) or KT5823 (1 μmol/l, a specific protein kinase G inhibitor). Two biotin switch based methods, two dimensional CyDye-maleimide difference gel electrophoresis (2D CyDye-maleimide DIGE) and SNO-resin-assisted capture (SNO-RAC), were utilized to identify SNO-modified proteins and sites. Using 2D CyDye-maleimide DIGE analysis, PostC was found to cause a 25% or greater increase in SNO of a number of proteins, which was blocked by treatment with L-NAME in parallel with the loss of protection. Using SNO-RAC, we identified 77 unique proteins with SNO sites after PostC. These results suggest that NO-mediated SNO signaling is involved in PostC-induced cardioprotection and these data provide the first set of candidate SNO proteins in PostC hearts.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number6
DOIs
StatePublished - Mar 15 2014

Keywords

  • Ischemic postconditioning
  • Nitric oxide
  • Protein S-nitrosylation
  • Soluble guanylyl cyclase/cGMP

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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