In vivo studies of altered expression patterns of p53 and proliferative control genes in chronic vitamin A deficiency and hypervitaminosis
| Autor: | Concha García, Teresa Barber, Luis Enrique Nores Torres, Gerardo López-Rodas, Elisa Borrás, Rosa Zaragozá, María Morante, Amparo Gimeno, Juan R. Viña, Vicente J. Miralles |
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| Rok vydání: | 2003 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Vitamin Retinyl Esters medicine.medical_specialty Macromolecular Substances Proto-Oncogene Proteins c-jun Receptors Retinoic Acid Blotting Western Retinoic acid Biology medicine.disease_cause Biochemistry chemistry.chemical_compound In vivo Cyclins Internal medicine medicine Animals Hypervitaminosis A RNA Messenger Rats Wistar Vitamin A Receptor Lung Differential display Reverse Transcriptase Polymerase Chain Reaction Vitamin A Deficiency Gene Expression Profiling DNA medicine.disease Hypervitaminosis Precipitin Tests Rats Vitamin A deficiency Endocrinology Gene Expression Regulation Liver chemistry Chronic Disease Immunology Diterpenes Tumor Suppressor Protein p53 Carcinogenesis Cell Division |
| Zdroj: | European Journal of Biochemistry. 270:1493-1501 |
| ISSN: | 1432-1033 0014-2956 |
| Popis: | Several clinical trials have revealed that individuals who were given beta-carotene and vitamin A did not have a reduced risk of cancer compared to those given placebo; rather, vitamin A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S. & Hammar, S. N. Engl. J. Med (1996) 334, 1150-1155; Hennekens, C.H., Buring, J.E., Manson, J.E., Stampfer, M., Rosner, B., Cook, N.R., Belanger, C., LaMotte, F., Gaziano, J.M., Ridker, P.M., Willet, W. & Peto, R. (1996) N. Engl. J. Med. 334, 1145-1149]. Using differential display techniques, an initial survey using rats showed that liver RNA expression of c-H-Ras was decreased and p53 increased in rats with chronic vitamin A deficiency. These findings prompted us to evaluate the expression of c-Jun, p53 and p21WAF1/CIF1 (by RT-PCR) in liver and lung of rats. This study showed that c-Jun levels were lower and that p53 and p21WAF1/CIF1 levels were higher in chronic vitamin A deficiency. Vitamin A supplementation increased expression of c-Jun, while decreasing the expression of p53 and p21WAF1/CIF1. Western-blot analysis demonstrated that c-Jun and p53 showed a similar pattern to that found in the RT-PCR analyses. Binding of retinoic acid receptors (RAR) to the c-Jun promoter was decreased in chronic vitamin A deficiency when compared to control hepatocytes, but contrasting results were found with acute vitamin A supplementated cells. DNA fragmentation and cytochrome c release from mitochondria were analyzed and no changes were found. In lung, an increase in the expression of c-Jun produced a significant increase in cyclin D1 expression. These results may explain, at least in part, the conflicting results found in patients supplemented with vitamin A and illustrate that the changes are not restricted to lung. Furthermore, these results suggest that pharmacological vitamin A supplementation may increase the risk of adverse effects including the risk of oncogenesis. |
| Databáze: | OpenAIRE |
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