PMID- 16520896
OWN - NLM
STAT- MEDLINE
DCOM- 20061211
LR  - 20060504
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 11
IP  - 3
DP  - 2006 Mar
TI  - ClC-3 chloride channel prevents apoptosis induced by thapsigargin in PC12 cells.
PG  - 327-36
AB  - 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.
FAU - Zhang, H-N
AU  - Zhang HN
AD  - Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, 74 
      Zhongshan 2 Road, Guangzhou, Guangdong, 510089, People's Republic of China.
FAU - Zhou, J-G
AU  - Zhou JG
FAU - Qiu, Q-Y
AU  - Qiu QY
FAU - Ren, J-L
AU  - Ren JL
FAU - Guan, Y-Y
AU  - Guan YY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Chloride Channels)
RN  - 0 (ClC-3 channel)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Caspase 3/metabolism
MH  - Cell Shape
MH  - Cell Size
MH  - Chloride Channels/genetics/*metabolism
MH  - DNA Fragmentation
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/*metabolism
MH  - Oligonucleotides, Antisense/genetics/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Thapsigargin/*metabolism
EDAT- 2006/03/08 09:00
MHDA- 2006/12/12 09:00
CRDT- 2006/03/08 09:00
PHST- 2006/03/08 09:00 [pubmed]
PHST- 2006/12/12 09:00 [medline]
PHST- 2006/03/08 09:00 [entrez]
AID - 10.1007/s10495-006-3980-2 [doi]
PST - ppublish
SO  - Apoptosis. 2006 Mar;11(3):327-36. doi: 10.1007/s10495-006-3980-2.