p53 protein and p21 mRNA levels and caspase-3 activity are altered by zinc status in aortic endothelial cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 283; no. 2; pp. C631 - C638
• Main Authors: Fanzo, Jessica C, Reaves, Scott K, Cui, Libin, Zhu, Lei, Lei, Kai Y
• Format: Journal Article
• Language: English
• Published: United States 01.08.2002
• Subjects: Aorta - cytology; Aorta - metabolism; bcl-2-Associated X Protein; Caspase 3; Caspase Inhibitors; Caspases - metabolism; Cell Nucleus - metabolism; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Genes, p53 - drug effects; Humans; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - genetics; Osmolar Concentration; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2 - genetics; RNA, Messenger - metabolism; Tumor Suppressor Protein p53 - genetics; Zinc - metabolism; Zinc - pharmacology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00248.2001

1  Department of Nutritional Sciences, University of Arizona, Tucson, Arizona 85721; and 2  Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742 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 µM 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 ~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. p53 tumor suppressor gene; apoptosis; zinc depleted; zinc supplemented; atherosclerosis