Abstract

This study aims to elucidate the signaling pathway for insulin-like growth factor-1 (IGF-1) in cultured neonatal rat cardiomyocytes and particularly the role of IGF-1 in cardiac apoptosis, IGF-1 stimulated polyphosphoinositide turnover, translocation of protein kinase C (PKC) isoforms (alpha, epsilon, and delta) from the soluble to the particulate fraction, activation of phospholipid-dependent and Ca2+-, phospholipid-dependent PKC, and activation of the extracellular-regulated kinase (ERK), IGF-1 attenuated sorbitol-induced cardiomyocyte viability and nuclear DNA fragmentation, These antiapoptotic effects of IGF-1 were blocked by PD098059 (an MEK inhibitor) but not by bisindolylmaleimide I (BIM, a specific PKC inhibitor), The ERK pathway may therefore be an important component in the mechanism whereby IGF-1 exerts its antiapoptotic effect on the cardiomyocyte, (C) 2000 Academic Press.