PMID- 8043004
OWN - NLM
STAT- MEDLINE
DCOM- 19940822
LR  - 20191210
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 301 ( Pt 2)
IP  - Pt 2
DP  - 1994 Jul 15
TI  - The intracellular Ca(2+)-pump inhibitors thapsigargin and cyclopiazonic acid 
      induce stress proteins in mammalian chondrocytes.
PG  - 563-8
AB  - Primary cultures of mammalian articular chondrocytes respond to treatment with 
      the intracellular Ca(2+)-pump inhibitors thapsigargin (TG) and cyclopiazonic acid 
      by specific changes in protein synthesis consistent with a stress response. 
      Two-dimensional gel electrophoresis of newly synthesized proteins confirmed that 
      the response was consistent with the induction of glucose-regulated proteins. The 
      effects of low-dose TG (10 nM), measured by changes in [35S]methionine labelling 
      of newly synthesized proteins, can first be observed by 10 h and are maximal by 
      24 h. The pattern of changes induced by TG is shared with cyclopiazonic acid, but 
      effects of both perturbants differ significantly from changes induced by heat 
      shock. Upon removal of TG, normal protein synthesis is restored by 48 h. 
      Immunoblots showed increased concentrations of the stress proteins HSP90, 
      HSP72/73 and HSP60 in chondrocytes treated with TG, but induction of newly 
      synthesized heat-shock proteins by TG was not apparent on 
      [35S]methionine-labelled gels. The alterations in protein synthesis induced by 
      Ca(2+)-pump inhibitors were unaffected by BAPTA-AM loading, which clamped 
      cytosolic Ca2+ at resting levels. We conclude that inhibition of intracellular 
      Ca(2+)-pump activity can elicit a stress response, which has important 
      implications for the interpretation of chronic use of Ca(2+)-pump inhibitors. In 
      particular, the activation of the cellular shock response should be considered in 
      interpreting the regulation of protein synthesis and cell survival by Ca(2+)-pump 
      inhibitors such as TG.
FAU - Cheng, T C
AU  - Cheng TC
AD  - Department of Anatomy, Physiology and Cell Biology, School of Veterinary 
      Medicine, University of California, Davis 95616.
FAU - Benton, H P
AU  - Benton HP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Indoles)
RN  - 0 (Terpenes)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - Calcimycin/pharmacology
MH  - Calcium/metabolism
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - Cartilage, Articular/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Heat-Shock Proteins/*biosynthesis
MH  - Hot Temperature
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Kinetics
MH  - Swine
MH  - Terpenes/*pharmacology
MH  - Thapsigargin
PMC - PMC1137118
EDAT- 1994/07/15 00:00
MHDA- 1994/07/15 00:01
PMCR- 1995/01/15
CRDT- 1994/07/15 00:00
PHST- 1994/07/15 00:00 [pubmed]
PHST- 1994/07/15 00:01 [medline]
PHST- 1994/07/15 00:00 [entrez]
PHST- 1995/01/15 00:00 [pmc-release]
AID - 10.1042/bj3010563 [doi]
PST - ppublish
SO  - Biochem J. 1994 Jul 15;301 ( Pt 2)(Pt 2):563-8. doi: 10.1042/bj3010563.