The possible mechanism of synergistic effects of ethanol, zinc and insulin on DNA synthesis in NIH 3T3 fibroblasts

In serum-starved NIH 3T3 fibroblast cultures, zinc (15-40 μM) enhanced both the individual and combined stimulatory effects of insulin and ethanol (EtOH) on DNA synthesis. Zinc, but not EtOH, also promoted the stimulatory effects of insulin on activating phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases. In the presence of zinc, insulin induced premature expression of cyclin E during early G1 phase; EtOH partially restored the normal timing (late G1 phase) of cyclin E expression. The results suggest that zinc and EtOH promote insulin-induced DNA synthesis by different mechanisms; while zinc acts by enhancing the effects of insulin on MAP kinase activation, EtOH may act by ensuring timely zinc-dependent insulin-induced expression of cyclin E. Copyright (C) 1999 Federation of European Biochemical Societies.