Extracellular regulated kinase, but not protein kinase C, is an antiapoptotic signal of insulin-like growth factor-1 on cultured cardiac myocytes

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