Specific induction of the 70-kD heat stress proteins by the tyrosine kinase inhibitor herbimycin-A protects rat neonatal

Heat shock protein (hsp) induction by stressful stimuli such as heat and ischemia is known to protect cardiac cells from severe stress. The ability to induce hsp’s in the heart directly by “nonstressful ” means would potentially have important clinical implications. In noncardiac cells, the tyrosine ki-nase inhibitor herbimycin-A has been shown to induce the 72-kD hsp. We therefore examined whether herbimycin-A and another tyrosine kinase inhibitor, genistein, could in-duce 70-kD hsp’s in primary cultures of rat neonatal cardio-myocytes, and whether these treatments protect against se-vere stress. Primary cardiomyocytes were incubated with herbimycin-A or genistein. hsp induction was measured 16– 20 h later by Western blotting. Cell survival after subse-quent lethal heat stress or simulated ischemia was assesse