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Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells

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Abstract

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 cytochrome c release 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.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (Key Grants Nos. 81230082, and 81370897, 81173055) and NSFC-CIHR, CHINA-CANADA Joint Health Research Initiative Proposal (No. 813111115).

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Authors and Affiliations

  1. Department of Pharmacology, and Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Jia-Wei Zeng, Xue-Lin Zeng, Ming-Ming Ma, Feng Yuan, Jie Liu, Xiao-Fei Lv, Guan-Lei Wang & Yong-Yuan Guan

  2. College of Life Science, Southern China Agriculture University, Guangzhou, 510642, People’s Republic of China

    Fei-Ya Li

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  1. Jia-Wei Zeng
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  2. Xue-Lin Zeng
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Correspondence to Guan-Lei Wang or Yong-Yuan Guan.

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Jia-Wei Zeng, Xue-Lin Zeng, Fei-Ya Li they equally contribute to this work

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Zeng, JW., Zeng, XL., Li, FY. et al. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells. Apoptosis 19, 1317–1329 (2014). https://doi.org/10.1007/s10495-014-1014-z

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