ClC-3 chloride channel prevents apoptosis induced by thapsigargin in PC12 cells |
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Authors: | H-N Zhang J-G Zhou Q-Y Qiu J-L Ren Y-Y Guan |
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Institution: | (1) Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan 2 Road, Guangzhou, Guangdong, 510089, People's Republic of China |
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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.
These authors contributed equally to this work. |
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Keywords: | apoptosis antisense chloride channel ClC-3 PC12 cells thapsigargin |
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