Induction of HSP70 in cultured rat neonatal cardiomyocytes by hypoxia and metabolic stress.
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.


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.
Department of Medicine, University of California, San Diego.
K
K
Iwaki
S H
SH
Chi
W H
WH
Dillmann
R
R
Mestril
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012966:Sodium Cyanide / Q000494:pharmacology
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D012966:Sodium Cyanide