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ClC-3 chloride channel prevents apoptosis induced by thapsigargin in PC12 cells

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Abstract

Cell volume can be altered by two different ways, swelling and shrinkage. Cell swelling is regulated by volume-regulated Cl− channel (VRC). It is not well understood whether shrinkage is regulated by VRC. We previously found that antisense oligonucleotide specific to ClC-3 (ClC-3 antisense) prevented cell proliferation, which was related to cell swell volume regulation. In the present study, we further studied the role of ClC-3 Cl− channel in cell apoptosis which was related to cell shrinkage volume regulation by using antisense oligonucleotide specific to ClC-3 (ClC-3 antisense) and ClC-3 cDNA transfection techniques. We found that thapsigargin (TG), a specific inhibitor of the endoplasmic reticulum calcium ATPase, evoked apoptotic morphological changes (including cytoplasmic blebbing, condensation of nuclear chromatin, and the formation of apoptotic bodies), DNA laddering, and caspase-3 activation in PC12 cells (Pheochromocytoma-derived cell line). TG increased the cell apoptotic population with a decrease in cell viability. These effects were consistent with the decrease in endogenous ClC-3 protein expression, which was also induced by TG. Overexpression of ClC-3 significantly inhibited TG effect on PC12 cell apoptosis, whereas the ClC-3 antisense produced opposite effects and facilitated apoptosis induced by TG. Our data strongly suggest that ClC-3 channel in PC12 cells mediates TG-induced apoptotic process through inhibitory mechanism. Thus, it appears that ClC-3 Cl− channel mediates both cell proliferation and apoptosis through accelerative and inhibitory fashions, respectively.

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Authors and Affiliations

  1. Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan 2 Road, Guangzhou, Guangdong, 510089, People's Republic of China

    H.-N. Zhang, J.-G. Zhou, Q.-Y. Qiu, J.-L. Ren & Y.-Y. Guan

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  1. H.-N. Zhang
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  2. J.-G. Zhou
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  3. Q.-Y. Qiu
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  4. J.-L. Ren
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  5. Y.-Y. Guan
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Correspondence to Y.-Y. Guan.

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These authors contributed equally to this work.

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Zhang, HN., Zhou, JG., Qiu, QY. et al. ClC-3 chloride channel prevents apoptosis induced by thapsigargin in PC12 cells. Apoptosis 11, 327–336 (2006). https://doi.org/10.1007/s10495-006-3980-2

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  • DOI: https://doi.org/10.1007/s10495-006-3980-2

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