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Title: Characterization of the sex-dependent myocardial S-nitrosothiol proteome.

Authors: Shao, Qin; Fallica, Jonathan; Casin, Kevin M; Murphy, Elizabeth; Steenbergen, Charles; Kohr, Mark J

Published In Am J Physiol Heart Circ Physiol, (2016 Feb 15)

Abstract: 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 F1FO-ATPase 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 Ca(2+)-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.

PubMed ID: 26702143 Exiting the NIEHS site

MeSH Terms: Animals; Coronary Circulation/drug effects*; Cyclophilin D; Cyclophilins/metabolism; Endoplasmic Reticulum/metabolism; Female; Heart/drug effects*; Male; Mice; Mice, Inbred C57BL; Myocardial Reperfusion Injury/metabolism; Myocardium/metabolism; Nitric Oxide Synthase Type III/biosynthesis; Nitric Oxide/biosynthesis; Phosphorylation; Proteome/drug effects*; S-Nitrosothiols/metabolism*; Sex Characteristics

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