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 different low Zn (ZD) media, Zn-free Opti-MEM and a ZD medium containing Chelex-100 treated serum, were used to deplete cellular zinc over one passage. Cellular zinc levels of ZD cells were significantly lower than in their controls 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 with their respective controls. To examine whether the effects were specific to zinc depletion, a third, zinc-replenished group (ZDA) was included in the Opti-MEM study in which cells were cultured in ZD media for nearly one passage before a change was made to zinc-adequate (ZA) medium for the last 24 h, Zinc levels in the ZDA cells were significantly higher than in ZD cells, and p53 mRNA abundance was normalized to control levels. Nuclear p53 protein levels were >100% higher in the ZD Opti-MEM cells than in ZA cells. Interestingly, the ZDA Opti-MEM cells had significantly lower levels of nuclear p53 protein than both the ZA and ZD cells. These data suggest that expression of p53, a critical component in the maintenance of genomic stability, may be affected by reductions in cellular zinc.