Characterization of the sex-dependent myocardial S-nitrosothiol proteome

Qin Shao, Jonathan Fallica, Kevin M. Casin, Elizabeth Murphy, Charles Steenbergen, Mark J. Kohr

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Premenopausal women exhibit endogenous cardioprotective signaling mechanisms that are thought to result from the beneficial effects of estrogen, which we have shown to increase protein S-nitrosylation in the heart. S-nitrosylation is a labile protein modification that increases with a number of different forms of cardioprotection, including ischemic preconditioning. Herein, we sought to identify a potential role for protein S-nitrosylation in sex-dependent cardioprotection. We utilized a Langendorff- perfused mouse heart model of ischemia-reperfusion injury with male and female hearts, and S-nitrosylation-resin-assisted capture with liquid chromatography tandem mass spectrometry to identify S-nitrosylated proteins and modification sites. Consistent with previous studies, female hearts exhibited resilience to injury with a significant increase in functional recovery compared with male hearts. In a separate set of hearts, we identified a total of 177 S-nitrosylated proteins in female hearts at baseline compared with 109 S-nitrosylated proteins in male hearts. Unique S-nitrosylated proteins in the female group included the F1FOATPase and cyclophilin D. We also utilized label-free peptide analysis to quantify levels of common S-nitrosylated identifications and noted that the S-nitrosylation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a was nearly 70% lower in male hearts compared with female, with no difference in expression. Furthermore, we found a significant increase in endothelial nitric oxide synthase expression, phosphorylation, and total nitric oxide production in female hearts compared with males, likely accounting for the enhanced S-nitrosylation protein levels in female hearts. In conclusion, we identified a number of novel S-nitrosylated proteins in female hearts that are likely to contribute to sex-dependent cardioprotection.

Original languageEnglish (US)
Pages (from-to)H505-H515
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
StatePublished - Feb 2016


  • Cardioprotection
  • Endothelial nitric oxide synthase
  • Ischemia-reperfusion injury
  • S-nitrosoglutathione reductase
  • S-nitrosylation
  • Sex differences

ASJC Scopus subject areas

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


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