PMID- 9298978
OWN - NLM
STAT- MEDLINE
DCOM- 19971022
LR  - 20191210
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 138
IP  - 6
DP  - 1997 Sep 22
TI  - Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2.
PG  - 1219-28
AB  - The oncogene bcl-2 encodes a 26-kD protein localized to intracellular membranes, 
      including the ER, mitochondria, and perinuclear membrane, but its mechanism of 
      action is unknown. We have been investigating the hypothesis that Bcl-2 regulates 
      the movement of calcium ions (Ca2+) through the ER membrane. Earlier findings in 
      this laboratory indicated that Bcl-2 reduces Ca2+ efflux from the ER lumen in 
      WEHI7.2 lymphoma cells treated with the Ca2+-ATPase inhibitor thapsigargin (TG) 
      but does not prevent capacitative entry of extracellular calcium. In this report, 
      we show that sustained elevation of cytosolic Ca2+ due to capacitative entry is 
      not required for induction of apoptosis by TG, suggesting that ER calcium pool 
      depletion may trigger apoptosis. Bcl-2 overexpression maintains Ca2+ uptake in 
      the ER of TG-treated cells and prevents a TG-imposed delay in intralumenal 
      processing of the endogenous glycoprotein cathepsin D. Also, Bcl-2 overexpression 
      preserves the ER Ca2+ pool in untreated cells when extracellular Ca2+ is low. 
      However, low extracellular Ca2+ reduces the antiapoptotic action of Bcl-2, 
      suggesting that cytosolic Ca2+ elevation due to capacitative entry may be 
      required for optimal ER pool filling and apoptosis inhibition by Bcl-2. In 
      summary, the findings suggest that Bcl-2 maintains Ca2+ homeostasis within the 
      ER, thereby inhibiting apoptosis induction by TG.
FAU - He, H
AU  - He H
AD  - Departments of Medicine and Pharmacology, Case Western Reserve University, 
      Cleveland, Ohio 44106, USA.
FAU - Lam, M
AU  - Lam M
FAU - McCormick, T S
AU  - McCormick TS
FAU - Distelhorst, C W
AU  - Distelhorst CW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calcium/*metabolism/pharmacokinetics
MH  - Calcium-Transporting ATPases/metabolism
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Cytoplasm/metabolism
MH  - Endoplasmic Reticulum/*chemistry/enzymology
MH  - Enzyme Inhibitors/pharmacology
MH  - Homeostasis/*physiology
MH  - Lymphoma
MH  - Mice
MH  - Proto-Oncogene Proteins c-bcl-2/*metabolism
MH  - Thapsigargin/pharmacology
MH  - Time Factors
MH  - Tumor Cells, Cultured/chemistry/cytology/enzymology
PMC - PMC2132547
EDAT- 1997/09/23 00:00
MHDA- 1997/09/23 00:01
PMCR- 1998/03/22
CRDT- 1997/09/23 00:00
PHST- 1997/09/23 00:00 [pubmed]
PHST- 1997/09/23 00:01 [medline]
PHST- 1997/09/23 00:00 [entrez]
PHST- 1998/03/22 00:00 [pmc-release]
AID - 10.1083/jcb.138.6.1219 [doi]
PST - ppublish
SO  - J Cell Biol. 1997 Sep 22;138(6):1219-28. doi: 10.1083/jcb.138.6.1219.