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Estrogen protects cardiomyocytes against oxidative stress by upregulation of cystathionine γ lyase expression
Author(s) -
Zhu XiaoYan,
Wang Long,
Cong Binhai,
Zhao Wei,
Ni Xin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.919.4
Subject(s) - gene knockdown , cystathionine beta synthase , downregulation and upregulation , estrogen receptor , cardioprotection , estrogen , chemistry , cycloheximide , oxidative stress , cystathionine gamma lyase , antagonist , estrogen receptor beta , endogeny , protein kinase b , pharmacology , apoptosis , microbiology and biotechnology , endocrinology , medicine , receptor , biology , biochemistry , protein biosynthesis , cysteine , enzyme , ischemia , cancer , breast cancer , gene
The mechanisms of cardioprotective effects of estrogen are not fully understood. Hydrogen sulfide (H2S) is generated predominantly by cystathionine γ lyase (CSE) in myocardium, and has been implicated to have cardioprotective effects. Thus, we hypothesize that endogenous H2S contributes to the cardioprotective effects of estrogen. We found that 17β‐estradiol (E2) increased CSE expression in primary cultured neonatal cardiomyocytes, which was blocked by nonselective estrogen receptor (ER) antagonist ICI 182780 and ERα antagonist MPP, but not by ERβ selective antagonist THC. E2 increased cell survival, decreased caspase‐3 activation and increased Akt phosphorylation in the cells upon hydrogen peroxide treatment. The protective effects of E2 were blocked by either CSE specific inhibitor PAG or knockdown of CSE expression with siRNA. E2‐induced CSE expression was abolished by the protein synthesis inhibitor cycloheximide, suggesting requirement of additional factors. E2 significantly increased Sp1 expression. Importantly, siRNA‐mediated knockdown of Sp1 expression markedly inhibited E2‐mediated upregulation of CSE expression. In conclusion, our data suggest that the cardioprotection of estrogen against oxidative stress is through, at least in part, stimulating CSE expression in cardiomyocytes. CSE induction upon E2 treatment is mainly due to the increased expression of Sp1.