Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells.
复制标题
囊性纤维化跨膜电导调节器 (CFTR) 可防止基底动脉平滑肌细胞中过氧化氢诱导的细胞凋亡。
DOI：
10.1007/s10495-014-1014-z
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发表时间：
2014
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：
Zeng Jia-Wei;Zeng Xue-Lin;Li Fei-Ya;Ma Ming-Ming;Yuan Feng;Liu Jie;Lv Xiao-Fei;Wang Guan-Lei;Guan Yong-Yuan
囊性纤维化跨膜电导调节因子(CFTR)作为cAMP依赖的氯离子通道，已在多种细胞中得到研究。CFTR在血管平滑肌细胞中大量表达，并与血管张力调节密切相关。然而，CFTR在基底动脉血管平滑肌细胞(BASMCs)中的功能意义仍不清楚。越来越多的证据表明，CFTR在细胞凋亡中起直接作用，细胞凋亡参与了CF的几个主要病理事件，如炎症、肺损伤和胰腺功能不全。因此，我们研究了cftr在过氧化氢(H_2O_2)诱导BASMC凋亡过程中的作用。我们发现，过氧化氢诱导的细胞凋亡与内源性CFTR蛋白表达的显著降低是平行的。腺病毒介导的cftr特异性siRNA沉默CFTR进一步增强了H_2O_2诱导的BASMC损伤，线粒体细胞色素释放到细胞质，切割caspase-3和-9蛋白表达和氧化谷胱甘肽水平，而降低细胞存活率、Bc l-2/Bax比值、线粒体膜电位、总谷胱甘肽水平、超氧化物歧化酶和过氧化氢酶活性。Forsklin对CFTR的药理激活作用与此相反。这些结果有力地表明，CFTR可能通过cAMP和线粒体依赖的途径和调节内源性抗氧化防御系统来调控氧化应激相关的BASMC凋亡。
Cystic fibrosis transmembrane conductance regulator (CFTR) acts as a cAMP-dependent chloride channel, has been studied in various types of cells. CFTR is abundantly expressed in vascular smooth muscle cells and closely linked to vascular tone regulation. However, the functional significance of CFTR in basilar vascular smooth muscle cells (BASMCs) remains elusive. Accumulating evidence has shown the direct role of CFTR in cell apoptosis that contributes to several main pathological events in CF, such as inflammation, lung injury and pancreatic insufficiency. We therefore investigated the role of CFTR in BASMC apoptotic process induced by hydrogen peroxide (H2O2). We found that H2O2-induced cell apoptosis was parallel to a significant decrease in endogenous CFTR protein expression. Silencing CFTR with adenovirus-mediated CFTR specific siRNA further enhanced H2O2-induced BASMC injury, mitochondrial cytochromecrelease into cytoplasm, cleaved caspase-3 and -9 protein expression and oxidized glutathione levels; while decreased cell viability, the Bcl-2/Bax ratio, mitochondrial membrane potential, total glutathione levels, activities of superoxide dismutase and catalase. The pharmacological activation of CFTR with forskolin produced the opposite effects. These results strongly suggest that CFTR may modulate oxidative stress-related BASMC apoptosis through the cAMP- and mitochondria-dependent pathway and regulating endogenous antioxidant defense system.