Oxidant stress derails the cardiac connexon connection.
Oxidant stress derails the cardiac connexon connection.
复制标题
氧化应激破坏心脏连接子的连接。
DOI：
10.1172/jci41780
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Tomaselli,GordonF
中科院分区：
文献类型：
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作者：
Tomaselli,GordonF
连接蛋白43（Cx43）是在闰盘处电耦合心肌细胞的间隙连接的主要蛋白质组分。氧化应激、Cx43表达减少和亚细胞定位改变存在于多种形式的结构性心脏病中。Cx43的这些变化导致心室电传导的改变，并易患致命性心律失常。Smyth等人在本期JCI的研究中验证了氧化应激干扰连接子沿沿着微管向缝隙连接的前向运输的假设（见266页开始的相关文章）。失败的人心室肌表现出减少Cx43和微管帽蛋白EB 1在闰盘。氧化应激在成年小鼠心脏减少N-钙粘蛋白，EB 1和Cx43共定位。在HeLa细胞和新生小鼠心室肌细胞，过氧化物暴露从微管的正端和改变微管动力学的EB 1位移。突变破坏EB 1-微管蛋白相互作用模仿氧化应激的影响，包括减少表面Cx43的表达。这些数据提供了重要的新的分子见解Cx43在间隙连接的调节，并可能确定在患病的心脏细胞偶联保存的目标。
Connexin 43 (Cx43) is the major protein component of gap junctions that electrically couple cardiomyocytes at the intercalated disc. Oxidant stress, reduced Cx43 expression, and altered subcellular localization are present in many forms of structural heart disease. These changes in Cx43 lead to alterations in electrical conduction in the ventricle and predispose to lethal cardiac arrhythmias. In their study in this issue of theJCI, Smyth et al. tested the hypothesis that oxidant stress perturbs connexon forward trafficking along microtubules to gap junctions (see the related article beginning on page 266). Failing human ventricular myocardium exhibited a reduction in Cx43 and the microtubule-capping protein EB1 at intercalated discs. Oxidant stress in the adult mouse heart reduced N-cadherin, EB1, and Cx43 colocalization. In HeLa cells and neonatal mouse ventricular myocytes, peroxide exposure displaced EB1 from the plus ends of microtubules and altered microtubule dynamics. Mutational disruption of the EB1-tubulin interaction mimicked the effects of oxidant stress, including a reduction in surface Cx43 expression. These data provide important new molecular insights into the regulation of Cx43 at gap junctions and may identify targets for preservation of cellular coupling in the diseased heart.