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Zhang HN, Zhou JG, Qiu QY, Ren JL, Guan YY.
ClC-3
chloride channel prevents apoptosis induced by thapsigargin in
PC12 cells.
Apoptosis. 2006 Mar;11(3):327-36
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 , 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). thapsigargin
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
thapsigargin. Overexpression of ClC-3 significantly inhibited
thapsigargin effect on PC12 cell apoptosis, whereas the ClC-3
antisense produced opposite effects and facilitated apoptosis
induced by thapsigargin. Our data strongly suggest that ClC-3
channel in PC12 cells mediates thapsigargin-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.
PMID: 16520896
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