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Depression of p21 transcriptional process and cell growth is independent of p53 and p21 expression, respectively, in zinc‐deficient human hepatoblastoma HepG2 cells
Author(s) -
Wong Stephen H.K.,
Zhao Y.Q.,
Shih Rita S.M.,
Han ChungTing,
Schoene Norberta W.,
Lei Kai Y.
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1109-c
We previously reported a delayed G 1 /S cell cycle progression in zinc‐deficient HepG2 cells. Since p21 is one of the major cell cycle regulators, the influence of zinc status on its expression was examined. Cells were cultured for one passage in media with different zinc levels: < 0.1 and 0.4 μM as severe (ZD) and mild zinc‐deficient (ZD0.4) media, respectively; 4.0 μM as in most cell culture media (ZN); 16 μM as in normal human plasma zinc level (ZA); and 32 μM to represent human plasma zinc level attainable by oral supplementation (ZS). In both ZD and ZD0.4 cells, the p21 mRNA and nuclear protein levels as well as p21 promoter activity were repressed as compared to that of ZN control cells. However, they were not altered in ZA and ZS cells as compared to ZN cells. Moreover, the amount of acetylated histone 4 associated with promoter regions of p21 were also depressed in ZD and ZD0.4 cells. Furthermore, depressed p21 promoter activity and protein level in ZD remained unchanged with treatment of p53 inhibitor. Transfection of a construct consisted of a constitutive promoter fused with a full length p21 coding sequence in ZD cells, normalized p21 protein expression to that of the ZN cells, but failed to correct cell growth reduction. Similar transfection in ZN cells overexpressed p21 and repressed cell growth. Thus, the present data indicate that in zinc‐deficient HepG2 cells, the depressed p21 transcriptional process and cell growth is independent of p53 and p21 expression, respectively.