ClC-3 chloride channel prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through mitochondria dependent pathway
ClC-3 chloride channel prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through mitochondria dependent pathway
复制标题
ClC-3氯离子通道通过线粒体依赖性途径防止过氧化氢诱导的基底动脉平滑肌细胞凋亡
DOI：
10.1007/s10495-011-0584-2
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发表时间：
2011-05-01
期刊：
影响因子：
7.2
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
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作者：
Qian, Yan;Du, Yan-Hua;Guan, Yong-Yuan
ClC-3Cl（-）通道在细胞体积调节和细胞周期中起重要作用.在血管平滑肌细胞中，我们发现ClC-3参与ET-1诱导的细胞增殖。本研究旨在进一步探讨ClC-3Cl（-）通道在过氧化氢（H2 O2）诱导的大鼠基底动脉平滑肌细胞（BASMCs）凋亡中的作用及其机制。结果表明，过表达ClC-3能显著降低H2 O2处理的BASMCs的凋亡率，提高细胞存活率;而沉默ClC-3能显著提高H2 O2处理的BASMCs的凋亡率。ClC-3过表达降低细胞色素C释放和caspase-3活性，增加线粒体膜电位稳定性和Bcl-2/Bax比值，而ClC-3沉默则产生相反的作用。此外，我们证明了ClC-3的过表达减弱了BASMCs中LaminA（结构基质蛋白之一）的降解，而ClC-3的沉默促进了LaminA的降解。我们的数据表明，ClC-3 Cl（-）通道可以通过内源性线粒体途径调节H2 O2诱导的BASMCs凋亡。
ClC-3 Cl(-) channel plays an important role in cell volume regulation and cell cycle. In vascular smooth muscle cells, we have found that ClC-3 was involved in ET-1 induced cell proliferation. The present study was designed to further investigate the role of ClC-3 Cl(-) channel in H(2)O(2)-induced apoptosis and its underlying mechanisms in rat basilar arterial smooth muscle cell (BASMCs). By using ClC-3 cDNA and small interference RNA (siRNA) transfection strategy, it was found that overexpression of ClC-3 significantly decreased the apoptotic rate of H(2)O(2)-treated BASMCs and increased the cell viability, whereas silencing of ClC-3 with siRNA produced opposite effects and increased the apoptotic rate. ClC-3 overexpression decreased cytochrome C release and caspase-3 activation, and increased both the stability of mitochondrial membrane potential and the ratio of Bcl-2/Bax, whereas silencing of ClC-3 produced opposite effect. Furthermore, we demonstrated that overexpression of ClC-3 attenuated, whereas silencing of ClC-3 facilitated, the degradation of LaminA, one of the structural matrix proteins, in BASMCs. Our data suggest that ClC-3 Cl(-) channel can modulate H(2)O(2)-induced apoptosis in BASMCs via the intrinsic, mitochondrial pathway.