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Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats

Zhu, Xiaoyan MD, PhD1; Tang, Zhiping BSc2; Cong, Binhai MD, PhD1; Du, Jiankui BSc2; Wang, Changnan BSc1; Wang, Long BSc1; Ni, Xin MD, PhD1; Lu, Jianqiang MD, MSc2

doi: 10.1097/GME.0b013e3182874732
Original Study

Objective: Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17β-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status.

Methods: Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 μg/kg/d) or vehicle for 12 weeks. At the end of the 12-week treatment, CSE expression, H2S generation, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, interleukin (IL)-6 concentration, and tumor necrosis factor-α (TNF-α) concentration in the left ventricle were determined.

Results: E2 increased CSE expression and H2S generation in the myocardium of ovariectomized rats. H2S production rate and serum E2 were positively correlated. E2 increased GSH/GSSG ratio, T-AOC, CAT, and SOD activity but decreased IL-6 and TNF-α levels. Serum E2 level was positively correlated with GSH/GSSG ratio, T-AOC, CAT, and SOD activity, and inversely correlated with IL-6 and TNF-α levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF-α levels.

Conclusions: E2 increases CSE expression and endogenous H2S generation in the myocardium. The effects of E2 are associated with decreased oxidative stress and inflammatory status. Our data suggest that estrogens might exert cardioprotective effects through up-regulation of CSE expression and H2S generation.

From the 1Department of Physiology, Second Military Medical University, Shanghai, China; and 2School of Kinesiology, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China.

Received October 23, 2012; revised and accepted January 10, 2013.

X.Z. and Z.T. contributed equally to this work.

Funding/support: This study was supported by the National Natural Science Foundation of China (grants 30971090, 31000516, and 31271270), the New Outstanding Young Scholar Program of Shanghai Health Bureau (XYQ2011045), and the Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Jianqiang Lu, MD, MSc, School of Kinesiology, Shanghai University of Sport, 399 Changhai Road, Shanghai 200438, China. E-mail: lujianqiang@sus.edu.cn; Xin Ni, MD, PhD, Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. E-mail: nixin@smmu.edu.cn

© 2013 by The North American Menopause Society.