p53 protein and p21 mRNA levels and caspase-3 activity are altered by zinc status in aortic endothelial cells |
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Authors: | Fanzo Jessica C Reaves Scott K Cui Libin Zhu Lei Lei Kai Y |
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Affiliation: | Department of Nutritional Sciences, University of Arizona, Tucson, Arizona 85721, USA. |
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Abstract: | The influence ofzinc status on the levels of p53, as well as downstream targetsof p53 in cell repair and survival, was examined in human aorticendothelial cells (HAECs). A serum-reduced low-zinc medium (ZD) wasused to deplete zinc over one passage. Other treatments includedzinc-normal control (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) treatment with 3.0, 16.0, and 32.0 µM zinc, respectively. Cellular zinc levels in the ZD cells were 64% of ZN controls; levelsin the ZA cells were not different, but levels in ZS cells weresignificantly higher (40%) than in ZN cells. No difference in p53 mRNAabundance was detected among all treatments; however, p53 nuclearprotein levels were >100% higher in the ZD and ZS cells and almost200% higher in the ZA cells than in ZN controls. In addition, p21 mRNAabundance, a downstream target of p53 protein, was increased in the ZScells compared with both the ZN control and ZD cells. In the ZS cells,bax and mcl-1 were also ~50% higher compared with ZN controls,whereas bcl-2 mRNA was increased compared with ZA cells. Moreover,caspase-3 activity of ZD cells was not different from that of ZNcontrols but was reduced to 83 and 69% of ZN controls in ZA and ZScells, respectively. Thus p53 protein and p53 downstream target genesappeared to be modulated by intracellular zinc status in HAECs. |
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