Expression of the p53 tumor suppressor gene is up-regulated by depletion of intracellular zinc in HepG2 cells

Expression and activation of the p53 tumor suppressor protein are modulated by various cellular stimuli. The objective of this work was to examine the influence of zinc depletion on the expression of p53 in HepG2 cells. Two d ifferent low Zn (ZD) media, Zn-free Opti-MEM and a ZD medium containing Che lex-100 treated serum, were used to deplete cellular zinc over one passage. Cellular zinc levels of ZD cells were significantly lower than in their co ntrols in both the Opti-MEM and Chelex studies. p53 mRNA abundance was 187% higher in ZD Opti-MEM cells and >100% higher in ZD Chelex cells compared w ith their respective controls. To examine whether the effects were specific to zinc depletion, a third, zinc-replenished group (ZDA) was included in t he Opti-MEM study in which cells were cultured in ZD media for nearly one p assage before a change was made to zinc-adequate (ZA) medium for the last 2 4 h, Zinc levels in the ZDA cells were significantly higher than in ZD cell s, and p53 mRNA abundance was normalized to control levels. Nuclear p53 pro tein levels were >100% higher in the ZD Opti-MEM cells than in ZA cells. In terestingly, the ZDA Opti-MEM cells had significantly lower levels of nucle ar p53 protein than both the ZA and ZD cells. These data suggest that expre ssion of p53, a critical component in the maintenance of genomic stability, may be affected by reductions in cellular zinc.