PMID- 8668330
OWN - NLM
STAT- MEDLINE
DCOM- 19960808
LR  - 20191210
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 12
IP  - 10
DP  - 1996 May 16
TI  - Bcl-2 inhibits hydrogen peroxide-induced ER Ca2+ pool depletion.
PG  - 2051-5
AB  - The mechanism by which Bcl-2 inhibits apoptosis is unknown. The Bcl-2 protein is 
      localized to intracellular membranes, including the endoplasmic reticulum (ER). 
      The ER is the major intracellular reservoir of Ca2+ in non-muscle cells, 
      sequestering Ca2+ for use in intracellular signaling, and is a prime target of 
      oxidative damage. Because of the recent suggestion that Bcl-2 acts in an 
      antioxidant pathway, we wondered whether Bcl-2 might protect the ER Ca2+ pool in 
      cells exposed to reactive oxygen species. To test this hypothesis, we assessed 
      the effect of hydrogen peroxide (H2O2) treatment on the ER Ca2+ pool in WEH17.2 
      cells, which do not express Bcl-2, and two stable transfectants, W.Hb13 and 
      W.Hb12. The Bcl-2 level by Western blotting is 4-fold higher in W.Hb12 cells 
      compared to W.Hb13 cells. The ER Ca2+ pool in H2O2-treated and untreated cells 
      was measured according to the amount of Ca2+ mobilized from the ER lumen into the 
      cytoplasm by thapsigargin (TG), a selective inhibitor of the ER (Ca2+)-ATPase. 
      H2O2 treatment produced a significant reduction in the TG-mobilizable Ca2+ pool 
      in WEH17.2 and W.Hb13 cells, but not in W.Hb12 cells, indicating that 
      overexpression of Bcl-2 preserves the integrity of the ER Ca2+ pool in cells 
      exposed to reactive oxygen species.
FAU - Distelhorst, C W
AU  - Distelhorst CW
AD  - Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, 
      USA.
FAU - Lam, M
AU  - Lam M
FAU - McCormick, T S
AU  - McCormick TS
LA  - eng
GR  - R01 CA42755-08/CA/NCI NIH HHS/United States
GR  - T32 CA59366/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antioxidants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Terpenes)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9007-49-2 (DNA)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - DNA/drug effects/metabolism
MH  - Endoplasmic Reticulum/*drug effects/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/*antagonists & inhibitors/pharmacology
MH  - Lymphoma/genetics/metabolism
MH  - Mice
MH  - Proto-Oncogene Proteins/genetics/metabolism/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Reactive Oxygen Species/pharmacology
MH  - Terpenes/pharmacology
MH  - Thapsigargin
MH  - Transfection
MH  - Tumor Cells, Cultured/drug effects
EDAT- 1996/05/16 00:00
MHDA- 1996/05/16 00:01
CRDT- 1996/05/16 00:00
PHST- 1996/05/16 00:00 [pubmed]
PHST- 1996/05/16 00:01 [medline]
PHST- 1996/05/16 00:00 [entrez]
PST - ppublish
SO  - Oncogene. 1996 May 16;12(10):2051-5.