Cultured neonatal rat heart cells can be preconditioned by ischemia, but not by heat shock. The role of stress proteins.
In this study we attempted to induce tolerance to simulated ischemia in beating cultured neonatal rat cardiomyocytes by subjecting them either to elevated temperatures or to a short period of simulated ischemia. This was done to investigate whether development of tolerance can be observed at the isolated, contracting myocyte level, as has been already described for intact organs: and whether the effect of preconditioning already become apparent during ischemia alone, as opposed to ischemia-reperfusion protocols. We find that no preconditioning can be achieved by a preceeding heat treatment. On the other hand, subjecting the cells to a non-lethal period of ischemia significantly reduces myocyte death during a second more severe ischemic insult. Both pretreatments induce elevated levels of the major fully inducible species of the hsp70 family, hsp68, making it unlikely that the presence of this protein is the sole determinant during preconditioning. The mRNA levels of several heat shock proteins (hsps) are increased by both treatments. However, these mRNAs are induced with different patterns, the most notable difference being the induction of hsp60 mRNA by ischemia, and the absence of this induction by heat shock. We further find that, contrary to some earlier reports, simulated ischemia activates the heat shock transcription factor (HSF) rapidly, as is the case for heat shock.
Ovelgönne
J H
JH
Department of Molecular Cell Biology, Utrecht University, The Netherlands.
Van Wijk
R
R
Verkleij
A J
AJ
Post
J A
JA
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014157:Transcription Factors