IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress

In this study we have determined the ability of IGF-1 to protect cardiac fi broblasts against osmotic-induced apoptosis and investigated the potential mechanism(s) underlying this protection. Treatment with IGF-1 (1-100 ng/ml) promoted a dose dependent increase in cell survival against osmotic cell d eath. Both Akt and ERK1/2 were rapidly phosphorylated by IGF-1 and blocked by wortmannin and PD98059, inhibitors of their upstream activators respecti vely. However, IGF-l-induced protection was mediated via a wortmannin-depen dent but PD98059-independent pathway as determined by cell survival assay s uggesting a role of PI3-K/Akt. Furthermore, IGF-1 appeared to reduce the ac tivation of a number of early components in the apoptotic pathway in a wort mannin dependent manner including the osmotic stress-induced perturbation i n mitochondrial membrane potential, cleavage and activation of caspase-3 an d DNA fragmentation. Thus, the results suggest that IGF-1 regulates osmotic stress-induced apoptosis via the activation of the PI3-K/Akt pathway at a point upstream of the mitochondria and caspase-3. (C) 2000 Academic Press.