p53 protein and p21 mRNA levels and caspase-3 activity are altered by zinc status in aortic endothelial cells.
The influence of zinc status on the levels of p53, as well as downstream targets of p53 in cell repair and survival, was examined in human aortic endothelial cells (HAECs). A serum-reduced low-zinc medium (ZD) was used to deplete zinc over one passage. Other treatments included zinc-normal control (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) treatment with 3.0, 16.0, and 32.0 microM zinc, respectively. Cellular zinc levels in the ZD cells were 64% of ZN controls; levels in the ZA cells were not different, but levels in ZS cells were significantly higher (40%) than in ZN cells. No difference in p53 mRNA abundance was detected among all treatments; however, p53 nuclear protein levels were >100% higher in the ZD and ZS cells and almost 200% higher in the ZA cells than in ZN controls. In addition, p21 mRNA abundance, a downstream target of p53 protein, was increased in the ZS cells compared with both the ZN control and ZD cells. In the ZS cells, bax and mcl-1 were also approximately 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 ZN controls but was reduced to 83 and 69% of ZN controls in ZA and ZS cells, respectively. Thus p53 protein and p53 downstream target genes appeared to be modulated by intracellular zinc status in HAECs.
Fanzo
Jessica C
JC
Department of Nutritional Sciences, University of Arizona, Tucson, Arizona 85721, USA.
Reaves
Scott K
SK
Cui
Libin
L
Zhu
Lei
L
Lei
Kai Y
KY
D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009994:Osmolar Concentration; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D061945:Caspase Inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015032:Zinc