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High zinc status in lung cells slows growth and induces DNA damage-induced gene expression
Date:2/25/2008

Researchers at the University of Maryland at College Park have discovered that Normal Human Bronchial Epithelial (NHBE) cells cultured in medium with elevated zinc level, at the high end of plasma zinc attainable by oral supplementation, demonstrated inhibition of cell growth, up-regulation of growth arrest and DNA damage-induced gene (Gadd45) mRNA and protein expression, and blockage of G2/M cell cycle progression. The research, published in the March 08 issue of the Experimental Biology and Medicine, demonstrated that the essential nutrient zinc, at elevated physiologic level, is capable of inducing stress responsive genes in the NHBE cells. NHBE cells function as a protective airway barrier and are representative of the cell population during lung tissue transformation and are considered to be progenitor cells for human bronchial cancer.

Gadd45 is ubiquitously expressed in response to genotoxic agents, and is involved in many biological processes related to the maintenance of genomic stability and apoptosis. Over expression of Gadd45 was found to induce G2/M cell cycle arrest. The importance of Gadd45 in G2/M regulation was further supported by findings of the inability of cells from Gadd45 knockout mice to arrest at the G2/M phase after exposure to UV radiation. In addition, a functional association between stress-activated mitogen-activated protein kinase p38 pathway and Gadd45 in response to environmental stresses has been established in past studies. Moreover, the dependence of Gadd45 induction for the normal function of the tumor suppressor gene p53, which plays an important role in the maintenance of genomic fidelity by controlling cell cycle checkpoints and apoptotic processes following cell exposure to genotoxic stress, is well established. Furthermore, in response to DNA damage, Gadd45 was found to contribute to the stability of p53.

The research team, led by David K. Y. Lei, a professor of Nutrition, and Rita S. M. Shih, a recent
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Contact: David K.Y. Lei
dlei@mail.umd.edu
301-405-2143
Society for Experimental Biology and Medicine
Source:Eurekalert

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