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

Junko Nakagawa; Masato Matsuoka

doi:10.1016/j.etap.2008.02.001

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

Environ Toxicol Pharmacol. 2008 Jul;26(1):109-12. doi: 10.1016/j.etap.2008.02.001. Epub 2008 Feb 12.

Authors

Junko Nakagawa¹, Masato Matsuoka

Affiliation

¹ Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

PMID: 21783897
DOI: 10.1016/j.etap.2008.02.001

Abstract

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.