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United States Department of Agriculture

Agricultural Research Service

Title: Zince Depletion Reduced Egr-1 Binding to Responsive Element and Apo a-I Promoter Activity in Hepg2 Cells

Authors
item Cui, Li Bin - UNIV. MD, COLLEGE PARK
item Schoene, Norberta
item Zhu, Lei - UNIV. MD, COLLEGE PARK
item Franco, Jessica - UNIV. MD, COLLEGE PARK
item Alshatwi, Ali - UNIV. MD, COLLEGE PARK
item Lei, K - UNIV. MD, COLLEGE PARK

Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 14, 2002
Publication Date: August 1, 2002
Citation: Cui, L., Schoene, N.W., Zhu, L., Franco, J.C., Alshatwi, A., Lei, K.Y. 2002. Zince depletion reduced egr-1 binding to responsive element and apo a-i promoter activity in hepg2 cells. American Journal of Physiology - Cell Physiology.

Interpretive Summary: Zinc, an essential micronutrient, is required by many enzymes involved in gene expression and, therefore, is vital in maintaining DNA, RNA, and protein synthesis in cells. An immediate effect of too little zinc in the diet is an impairment in cell growth and repair. Marginal zinc deficiencies result in reduced wound healing and declines in immune response in humans. Critical sites where zinc acts to control cellular function need to be more clearly identified and used as a basis for defining what is an adequate intake to maintain human health. Cells were grown in cultures containing amounts of zinc that simulated a range to reflect human consumption patterns. These included a deficient diet, a normal diet, and a super-adequate diet. Cells grown in the zinc deficient culturing medium where shown to make DNA very slowly and grow less rapidly than cells grown in culture media containing adequate and more than adequate amounts of zinc. A protein factor known to induce gene expression was also decreased in the zinc-deficient cells. The results expand on information that explains the role of zinc in regulating cell function. Increased knowledge about the function of zinc in preserving the health of the cell and the individual will benefit researchers working across a wide spectrum of the life sciences - from molecular and cell biologists to immunologists and nutritionists.

Technical Abstract: This study was designed to examine the influence of zinc status of HepG2 cells on the expression of Egr-1, a transcription factor that has been shown to be involved in the regulation of apoA-I gene expression. A low zinc media (ZD), consisting of DMEM and 10% Chelex-100 treated serum was used to deplete cellular zinc over one passage. In addition, cells were cultured for one passage in media containing: 4 micromolar zinc (ZN), which represents the normal zinc concentrations found in most culture media; 16.0 micromolar zinc (ZA), which represents normal human plasma zinc levels; or 32.0 micromolar zinc (ZS) for comparison to plasma zinc levels attainable by oral supplementation in humans. As compared to ZN cells, cellular zinc levels were 43% lower in ZD cells but 70% and 156% higher in ZA and ZS cells, respectively. DNA content per plate and the proportion of cells in S phase of cell cycles were significantly lower for ZD cells compared to the other three groups. Nuclear Egr-1 protein as well as its binding to the responsive element E1 (-196 to -174) of the apoA-1 gene promoter were markedly decreased in the ZD cells. This was associated with depressed apoA-I promoter activity in ZD cells compared to the other groups. Thus, the reduction in Egr-1 expression and binding to its responsive element in the apoA-I promoter may contribute to the down- regulation of apoA-I in zinc-deficient HepG2 cells.

Last Modified: 7/22/2014
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