Sex differences in cardiomyocyte connexin43 expression.
Sex differences in cardiomyocyte connexin43 expression.
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DOI：
10.1097/fjc.0b013e31821b70b4
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发表时间：
2011-07
影响因子：
3
通讯作者：
Sucharov CC
中科院分区：
文献类型：
--
作者：
Stauffer BL;Sobus RD;Sucharov CC
心脏连接蛋白43（Cx43）的减少在异常细胞间通讯中起关键作用，并与女性心脏对心律失常的抵抗力有关。因此，我们假设在病理条件下，女性心肌细胞中Cx43的表达高于男性心肌细胞。从雄性和雌性大鼠中分离成年心室肌细胞，并用苯肾上腺素（一种公认的病理刺激）处理。测定Cx43基因和蛋白表达。还测定了microRNA-1表达，一种已知控制心肌细胞中Cx43蛋白表达的microRNA。在基础和病理条件下，雌性心肌细胞中Cx43 mRNA和蛋白水平均显著高于雄性心肌细胞（mRNA：1.4倍;蛋白：5倍，均p< 0.05）。苯肾上腺素治疗增加Cx43的表达只在女性心肌细胞。雌鼠心肌细胞经苯肾上腺素处理后，Cx43磷酸化水平（Cx43功能保留的标志物）也升高（P<0.05），microRNA-1表达降低（P<0.05）。microRNA-1的表达在雄性心肌细胞中未被苯乙哌啶处理。因此，microRNA-1的性别差异可能是病理条件下心肌细胞中Cx43表达的性别差异的原因。综上所述，我们的结果表明，Cx43表达和位点特异性磷酸化的性别差异有利于女性心肌细胞的心脏保护。
Decreases in cardiac connexin43 (Cx43) play a critical role in abnormal cell to cell communication and have been linked to the resistance of the female heart to arrhythmias. We therefore hypothesized that Cx43 expression would be greater in female cardiomyocytes than male cardiomyocytes under pathologic conditions. Adult ventricular myocytes were isolated from male and female rats and treated with phenylephrine, a well established pathologic stimulus. Cx43 gene and protein expression was determined. microRNA-1 expression, a microRNA known to control Cx43 protein expression in cardiomyocytes, was also determined. Cx43 mRNA and protein levels were significantly higher in the female cardiomyocytes than the male cardiomyocytes (mRNA: 1.4-fold; Protein: 5-fold, both p< 0.05) under both basal and pathologic conditions. Phenylephrine treatment increased Cx43 expression only in female cardiomyocytes. Cx43 phosphorylation, a marker of preserved Cx43 function, was also higher (P<0.05) and microRNA-1 expression was lower (P<0.05) in the female cardiomyocytes after phenylephrine treatment. microRNA-1 expression was unchanged by phenylephrine treatment in male cardiomyocytes. Thus, a sex-difference in microRNA-1 may be responsible for the sex-difference in Cx43 expression in cardiomyocytes under pathologic conditions. Taken together our results demonstrate a sex-difference in Cx43 expression and site specific phosphorylation that favors cardioprotection in female cardiomyocytes.