Zinc Induces Expression of the BH3-only Protein PUMA Through p53 and ERK Pathways in SH-SY5Y Neuroblastoma Cells.
Neurochem Res. 2009 Feb 25;
Authors: Hara H, Kamiya T, Adachi T
Accumulating evidence suggests that zinc (Zn(2+)) contributes to neuronal death in pathologic states such as ischemia. p53-upregulated modulator of apoptosis (PUMA), which is a BH3-only protein, is known to promote apoptosis through a tumor suppressor p53-dependent and -independent mechanism. In this study, we examined the effect of Zn(2+) on the induction of the PUMA gene in human neuroblastoma SH-SY5Y cells. The expression of PUMA was induced by Zn(2+) in a dose- and time-dependent manner. A reporter assay revealed that Zn(2+) activated the PUMA promoter. In addition, the mutation of the p53 binding site in the PUMA promoter region reduced promoter activation by Zn(2+). These findings suggest that p53 participates in Zn(2+)-induced PUMA expression. Furthermore, we also demonstrated here that Zn(2+) stimulates the phosphorylation of ERK and that the MEK-ERK pathway inhibitor, U0126, suppressed Zn(2+)-induced PUMA expression. Taken together, these results indicate that Zn(2+) regulates the induction of PUMA through p53 and ERK pathways.
PMID: 19241161 [PubMed - as supplied by publisher]