PMID- 15451625
OWN - NLM
STAT- MEDLINE
DCOM- 20050308
LR  - 20061115
IS  - 0143-4160 (Print)
IS  - 0143-4160 (Linking)
VI  - 36
IP  - 5
DP  - 2004 Nov
TI  - Role of store-dependent influx of Ca2+ and efflux of K+ in apoptosis of CHO 
      cells.
PG  - 421-30
AB  - Agents mobilising Ca(2+) from the endoplasmic reticulum are known to activate 
      apoptosis. Whatever means are used, the release of Ca(2+) is often followed by a 
      store-dependent entry of Ca(2+). Whether apoptosis is triggered by the depletion 
      of the stores or by the subsequent store-dependent entry of Ca(2+) is still a 
      matter of controversy. Here we studied apoptosis in CHO cells transfected with 
      the rat neurotensin (NT) receptor, in which the store-dependent entry of Ca(2+) 
      is abolished by repressing the transient receptor potential channel 2 (TRPC2) by 
      an antisense oligonucleotide strategy (TRPC2(-) cells) [Cell Calcium 30 (2001) 
      157]. When stimulated with thapsigargin (TG), apoptosis occurred in both TRPC2(+) 
      and TRPC2(-) cells but 12h earlier in TRPC2(+) cells, suggesting that 
      store-dependent entry of Ca(2+) can accelerate the process. The expression and 
      localisation of caspase-12, an enzyme that has been involved in the apoptosis 
      triggered by a stress on the endoplasmic reticulum, was not different in TRPC2(+) 
      and TRPC2(-) cells. On the contrary, the expression of GADD153 (Growth Arrest and 
      DNA Damage inducible gene 153) triggered by TG treatment depended on external 
      Ca(2+) and occurred earlier in TRPC2(+) than in TRPC2(-) cells. In these cells, 
      we also noted the presence of K(+) channels activated by Ca(2+) (K(Ca) channels). 
      Stimulation of TRPC2(+) cells with TG or with NT triggered a long sustained K(+) 
      current, parallel to [Ca(2+)](i) transients, and resulting in a sustained 
      hyperpolarisation of the cell membrane. K(+) current and hyperpolarisation were 
      transient and not sustained in TRPC2(-) cells. Inhibition of K(Ca) channels with 
      charybdotoxin dramatically reduced the K(+) current and also significantly 
      brought down the level of apoptosis, suggesting that a prolonged efflux of K(+) 
      could be involved in the apoptosis process. We conclude that in CHO cells, 
      store-dependent entry of Ca(2+) can accelerate apoptosis by accelerating the 
      expression of GADD153 and by inducing a prolonged efflux of K(+) out of the cell.
FAU - Pigozzi, Delphine
AU  - Pigozzi D
AD  - Departement de Physiologie, Universite Catholique de Louvain, 55/40 av. 
      Hipppocrate, Brussels B-1200, Belgium.
FAU - Tombal, Bertrand
AU  - Tombal B
FAU - Ducret, Thomas
AU  - Ducret T
FAU - Vacher, Pierre
AU  - Vacher P
FAU - Gailly, Philippe
AU  - Gailly P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Membrane Proteins)
RN  - 0 (Potassium Channels, Calcium-Activated)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Trpc2 protein, rat)
RN  - 115422-61-2 (Charybdotoxin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - CHO Cells
MH  - Calcium Signaling/drug effects/*physiology
MH  - Charybdotoxin/pharmacology
MH  - Cricetinae
MH  - Membrane Proteins/antagonists & inhibitors/genetics/*physiology
MH  - Potassium Channels, Calcium-Activated/antagonists & 
      inhibitors/genetics/physiology
MH  - TRPC Cation Channels
MH  - Transfection/methods
EDAT- 2004/09/29 05:00
MHDA- 2005/03/09 09:00
CRDT- 2004/09/29 05:00
PHST- 2003/07/07 00:00 [received]
PHST- 2004/02/20 00:00 [revised]
PHST- 2004/04/05 00:00 [accepted]
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2005/03/09 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
AID - S0143416004000880 [pii]
AID - 10.1016/j.ceca.2004.04.002 [doi]
PST - ppublish
SO  - Cell Calcium. 2004 Nov;36(5):421-30. doi: 10.1016/j.ceca.2004.04.002.