Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Apoptosis. 2011 May;16(5):468-77. doi: 10.1007/s10495-011-0584-2.
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.
ClC-3 Cl(-) 通道在细胞体积调节和细胞周期中发挥重要作用。在血管平滑肌细胞中，我们发现 ClC-3 参与了 ET-1 诱导的细胞增殖。本研究旨在进一步探讨 ClC-3 Cl(-) 通道在 H₂O₂诱导的大鼠基底动脉平滑肌细胞 (BASMCs) 凋亡中的作用及其潜在机制。通过使用 ClC-3 cDNA 和小干扰 RNA (siRNA) 转染策略，发现 ClC-3 的过表达显著降低了 H₂O₂处理的 BASMCs 的凋亡率，增加了细胞活力，而 ClC-3 的 siRNA 沉默则产生了相反的效果，增加了凋亡率。ClC-3 的过表达减少了细胞色素 C 的释放和 caspase-3 的激活，增加了线粒体膜电位的稳定性和 Bcl-2/Bax 的比值，而 ClC-3 的沉默则产生了相反的效果。此外，我们证明了 ClC-3 的过表达减弱了，而 ClC-3 的沉默促进了，BASMCs 中结构基质蛋白之一的 LaminA 的降解。我们的数据表明，ClC-3 Cl(-) 通道可以通过内在的线粒体途径调节 H₂O₂诱导的 BASMCs 凋亡。
