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The activation of protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate is blocked by tyrosine kinase inhibition and reduced by preconditioning in rat neonatal heart.
Previous studies have shown that the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) induces an upregulation of protein kinase C (PKC) activity in neonatal rat hearts and reduces the delayed arrhythmic response to ischemia/reperfusion. To determine whether activation of tyrosine kinases or inhibition of protein tyrosine phosphatases (PTPs) are involved in the TPA-mediated increase in PKC, hearts from neonatal rats were incubated in tyrosine kinase inhibitor genistein (3 micromol/L) or a combination of genistein with sodium orthovanadate (100 micromol/L) for 2 hours before ischemia/reperfusion. The ischemia/reperfusion-elicited decrease in ventricular function was monitored using sonomicrometry. The decrease in contractility evoked by ischemia/reperfusion was markedly inhibited in hearts preincubated with genistein or with both genistein and orthovanadate, but the decrease in ventricular size was not inhibited by either treatment. These results suggest that the activation of tyrosine kinases and inhibition of PTPs play a major role in the TPA-mediated upregulation of PKC activity in neonatal rat hearts and may be related to the mechanism of preconditioning-mediated cardioprotection.Q:

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