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Zinco. O zinco induz bloqueio na Fase G2/M do ciclo celular dependente do
gene p53 e p21 nas células epiteliais brônquicas normais. A deficiência de
zinco propicia o crescimento do carcinoma brônquico
16/09/10
A concentração normal de zinco provoca aumento da proteína p53 a qual induz aumento da p21 e protege o pulmão do
carcinoma brônquico provocado pelos poluentes que respiramos constantemente em nossa cidade de São Paulo.
José de Felippe Junior
Zinc-induced G2/M blockage is p53 and p21 dependent in normal human bronchial epithelial cells.
Wong SH, Shih RS, Schoene NW, Lei KY. Am J Physiol Cell Physiol. 2008 Jun;294(6):C1342-9.
Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.
Abstract
The involvement of p53 and p21 signal pathway in the G2/M cell cycle progression of zinc-supplemented normal human bronchial
epithelial (NHBE) cells was examined using the small interferring RNA (siRNA) approach. Cells were cultured for one passage in a
different concentration of zinc: <0.4 microM (ZD) as zinc deficient; 4 microM as normal zinc level (ZN) in culture medium; 16 microM
(ZA) as normal human plasma zinc level; and 32 microM (ZS) as the high end of plasma zinc attainable by oral supplementation.
Nuclear p21 protein and mRNA levels as well as promoter activity in ZS cells, but not in ZD cells, were markedly elevated to almost
twofold compared with ZN control cells. G2/M blockage in ZS cells was coupled with the observation of elevated p21 gene expression.
In ZS cells, the abrogation of p21 protein induction by the transfection of p21 siRNA was shown to alleviate the G2/M blockage,
demonstrating the positive linkage of p21 elevation and G2/M blockage. Abolishment of the increase in p53 protein in ZS cells with
transfection of p53 siRNA normalized the elevated p21 protein to a similar level as in ZN control cells, which demonstrated that the p21
induction is p53 dependent. Furthermore, the normalization of p53 protein by siRNA treatment in ZS cells alleviated cell growth
depression and G2/M blockage, which demonstrated that p53 was involved in the high zinc status-induced G2/M blockage and growth
depression. Thus high zinc status in NHBE cells upregulates p53 expression which in turn elevates p21 that eventually induces G2/M
blockage.
PMID: 18353898
3/10/2011 14:27