INDUCTION OF HSP70 IN CULTURED RAT NEONATAL CARDIOMYOCYTES BY HYPOXIAAND METABOLIC STRESS

Background. A cultured neonatal rat cardiomyocyte model is used to inv estigate the expression of the inducible heat shock protein 70 (HSP70i ) during hypoxia/reoxygenation and metabolic stress. Methods and Resul ts. The major HSP70i is increased in its expression at the mRNA and pr otein level in myocytes exposed to hypoxia/reoxygenation and metabolic stress by the addition of 2-deoxyglucose and sodium cyanide, which ar e inhibitors known to block ATP production. Surprisingly, the appearan ce of HSP70 mRNA precedes the intracellular ATP depletion caused by hy poxia, which is contrary to what we observe when the cardiomyocytes ar e subjected to metabolic stress. Conclusions. It has been postulated r ecently that the decrease in intracellular ATP content in cells under stress may be the trigger that leads to the induction of HSP70i by red ucing 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 stag es 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 indicat es that cardiomyocytes are able to respond to hypoxia/reoxygenation an d metabolic stress with increased HSP70i production and points to a po tential protective role of heat shock proteins during ischemia/reperfu sion injury.