Suppression of zinc-induced p53 phosphorylation and p21 expression by wortmannin in A549 human pulmonary epithelial cells.

In A549 cells treated with zinc sulfate (ZnSO(4)), the levels of p53 phosphorylated at Ser15 and total p53 protein increased. Treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K)-related kinases, suppressed ZnSO(4)-induced phosphorylation and accumulation of p53 protein. Expression of cyclin-dependent kinase inhibitor p21, one of the genes regulated by p53, was up-regulated following exposure to ZnSO(4), and suppressed by preincubation with wortmannin. These results suggest that zinc might induce the phosphorylation of p53 at Ser15 through wortmannin-sensitive pathway(s) at least in part, and result in the transactivation of the p21 gene in this human pulmonary epithelial cell line.