Zinc status affects p53, gadd45, and c-fos expression and caspase-3 activity in human bronchial epithelial cells

This study was designed to examine theinfluence of zinc depletion and supplementation on the expression ofp53 gene, target genes of p53, andcaspase-3 activity in normal human bronchial epithelial (NHBE) cells. Aserum-free, low-zinc medium containing 0.4 µmol/l of zinc zincdeficient (ZD)] was used to deplete cellular zinc over one passage. Inaddition, cells were cultured for one passage in media containing 4.0 µmol/l of zinc zinc normal (ZN)], which represents normal cultureconcentrations (Clonetics); 16 µmol/l of zinc zinc adequate (ZA)],which represents normal human plasma zinc levels; or 32 µmol/l ofzinc zinc supplemented (ZS)], which represents the high end ofplasma zinc levels attainable by oral supplementation in humans.Compared with ZN cells, cellular zinc levels were 76% lower in ZDcells but 3.5-fold and 6-fold higher in ZA and ZS cells, respectively.Abundances of p53 mRNA and nuclear p53 protein were elevatedin treatment groups compared with controls (ZN). For p53mRNA abundance, the highest increase (3-fold) was observed in ZD cells.In contrast, the highest increase (17-fold) in p53 nuclearprotein levels was detected in ZS cells. Moreover, gadd45mRNA abundance was moderately elevated in ZD and ZA cells and was notaltered in ZS cells compared with ZN cells. Furthermore, the onlyalteration in c-fos mRNA and caspase-3 activity was thetwofold increase and the 25% reduction, respectively, detected in ZScompared with ZN cells. Thus p53, gadd45, andc-fos and caspase-3 activity appeared to be modulated bycellular zinc status in NHBE cells.