PMID- 9705090
OWN - NLM
STAT- MEDLINE
DCOM- 19981015
LR  - 20191210
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 139
IP  - 1-2
DP  - 1998 Apr 30
TI  - Apoptosis induction by the glucocorticoid hormone dexamethasone and the 
      calcium-ATPase inhibitor thapsigargin involves Bc1-2 regulated caspase 
      activation.
PG  - 229-38
AB  - The requirement for caspases (ICE-like proteases) were investigated in mediating 
      apoptosis of WEHI7.2 mouse lymphoma cells in response to two death inducers with 
      different mechanisms of action, the glucocorticoid hormone dexamethasone (DX) and 
      the calcium-ATPase inhibitor thapsigargin (TG). Apoptosis induction by these 
      agents followed different kinetics, and was closely correlated with in vivo 
      activation of caspase-3 (CPP32/Yama/Apopain) and cleavage of the caspase target 
      protein poly(ADP-ribose) polymerase (PARP). Caspase activation and PARP cleavage 
      were inhibited by Bcl-2 overexpression. Cell extracts from DX- and TG-treated 
      cells cleaved the in vitro synthesized baculovirus p35 ICE-like protease target, 
      producing 25 and 10 kDa fragments. p35 cleavage was inhibited by mutating the 
      active site aspartic acid to alanine, and by a panel of protease inhibitors that 
      inhibit caspase-3-like proteases, including iodoacetamide, N-ethylmaleimide, and 
      Ac-DEVD-cho. Treatment of cells in vivo with two cell permeant peptide 
      fluoromethylketone inhibitors of caspase activity, Z-VAD-fmk and Z-DEVD-fmk, 
      inhibited DX- and TG-induced apoptotic nuclear changes and maintained plasma 
      membrane integrity, whereas the cathepsin inhibitor, Z-FA-fmk, and two calpain 
      inhibitors failed to inhibit apoptosis. An unexpected observation was that due to 
      the delayed time course of DX-induced apoptosis, optimal preservation of plasma 
      membrane integrity was achieved by adding caspase inhibitors beginning 8 h after 
      DX addition. In summary, the findings indicate that two diverse 
      apoptosis-inducing signals converge into a common Bcl-2-regulated pathway that 
      leads to caspase activation and apoptosis.
FAU - McColl, K S
AU  - McColl KS
AD  - Department of Medicine, Case Western Reserve University/Ireland Cancer Center, 
      Cleveland, OH 44106-4937, USA.
FAU - He, H
AU  - He H
FAU - Zhong, H
AU  - Zhong H
FAU - Whitacre, C M
AU  - Whitacre CM
FAU - Berger, N A
AU  - Berger NA
FAU - Distelhorst, C W
AU  - Distelhorst CW
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, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glucocorticoids)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Viral Proteins)
RN  - 0 (inhibitor of apoptosis, Nucleopolyhedrovirus)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Caspase 3
MH  - *Caspases
MH  - Cell Death/drug effects
MH  - Cell Membrane
MH  - Cysteine Endopeptidases/*metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Dexamethasone/*pharmacology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Glucocorticoids/pharmacology
MH  - Inhibitor of Apoptosis Proteins
MH  - Lymphoma
MH  - Mice
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/*physiology
MH  - Thapsigargin/*pharmacology
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Viral Proteins/genetics/metabolism
EDAT- 1998/08/15 00:00
MHDA- 1998/08/15 00:01
CRDT- 1998/08/15 00:00
PHST- 1998/08/15 00:00 [pubmed]
PHST- 1998/08/15 00:01 [medline]
PHST- 1998/08/15 00:00 [entrez]
AID - S0303-7207(98)00051-3 [pii]
AID - 10.1016/s0303-7207(98)00051-3 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 1998 Apr 30;139(1-2):229-38. doi: 
      10.1016/s0303-7207(98)00051-3.