Document Detail

Induction of HSP70 in cultured rat neonatal cardiomyocytes by hypoxia and metabolic stress.
MedLine Citation:
PMID:  8504517     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: A cultured neonatal rat cardiomyocyte model is used to investigate the expression of the inducible heat shock protein 70 (HSP70i) during hypoxia/reoxygenation and metabolic stress. METHODS AND RESULTS: The major HSP70i is increased in its expression at the mRNA and protein level in myocytes exposed to hypoxia/reoxygenation and metabolic stress by the addition of 2-deoxyglucose and sodium cyanide, which are inhibitors known to block ATP production. Surprisingly, the appearance of HSP70 mRNA precedes the intracellular ATP depletion caused by hypoxia, which is contrary to what we observe when the cardiomyocytes are subjected to metabolic stress. CONCLUSIONS: It has been postulated recently that the decrease in intracellular ATP content in cells under stress may be the trigger that leads to the induction of HSP70i by reducing the pool of free HSP70, thus activating the stress response. Our results indicate that although this may be the case during metabolic stress, another route of activation must be used during the early stages of hypoxia in cardiomyocytes. The induction of HSP70i also appears to precede the onset of cellular damage as measured by the release of cytoplasmic enzymes and preincorporated arachidonic acid. This indicates that cardiomyocytes are able to respond to hypoxia/reoxygenation and metabolic stress with increased HSP70i production and points to a potential protective role of heat shock proteins during ischemia/reperfusion injury.
K Iwaki; S H Chi; W H Dillmann; R Mestril
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  87     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-07-02     Completed Date:  1993-07-02     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2023-32     Citation Subset:  AIM; IM    
Department of Medicine, University of California, San Diego.
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MeSH Terms
Adenosine Triphosphate / physiology
Animals, Newborn
Cell Hypoxia / physiology
Cells, Cultured
Deoxyglucose / pharmacology
Gene Expression
Heat-Shock Proteins / genetics,  metabolism*
Myocardial Reperfusion Injury / metabolism*
Myocardium / cytology,  metabolism*
RNA, Messenger / genetics
Rats, Sprague-Dawley
Sodium Cyanide / pharmacology
Grant Support
Reg. No./Substance:
0/Heat-Shock Proteins; 0/RNA, Messenger; 143-33-9/Sodium Cyanide; 154-17-6/Deoxyglucose; 56-65-5/Adenosine Triphosphate

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