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

In serum-starved NIH 3T3 fibroblast cultures, zinc (15-40 mu M) enhanced bo th the individual and combined stimulatory effects of insulin and ethanol ( EtOH) on DNA synthesis. Zinc, but not EtOH, also promoted the stimulatory e ffects of insulin on activating phosphorylation of p42/p44 mitogen-activate d 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 t hat zinc and EtOH promote insulin-induced DNA synthesis by different mechan isms; while zinc acts by enhancing the effects of insulin on MAP kinase act ivation, EtOH may act by ensuring timely zinc-dependent insulin-induced exp ression of cyclin E, (C) 1999 Federation of European Biochemical Societies.