期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 310, 期 4, 页码 H505-H515出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00681.2015
关键词
sex differences; ischemia-reperfusion injury; cardioprotection; S-nitrosylation; endothelial nitric oxide synthase; S-nitrosoglutathione reductase
资金
- National Natural Science Foundation of China [81270374, 81570390]
- China Scholarship Council
- NHLBI/National Institutes of Health (NIH) Intramural Program [ZIA-HL-002065]
- NIH [T32-ES-0741, R01-HL-039752, R00-HL-114721]
- American Heart Association [12BGIA11780030]
- National Natural Science Foundation of China [81270374, 81570390]
- China Scholarship Council
- NHLBI/National Institutes of Health (NIH) Intramural Program [ZIA-HL-002065]
- NIH [T32-ES-0741, R01-HL-039752, R00-HL-114721]
- American Heart Association [12BGIA11780030]
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 Langen-dorff-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 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.
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