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Molecular modifications of cholesterol metabolism in the liver and the brain after chronic contamination with cesium 137
Authors:R. Racine,L. Grandcolas,S. Grison,P. Gourmelon,Y. Gué  guen,G. Veyssiè  re,M. Souidi
Affiliation:1. Institute for Radiological Protection and Nuclear Safety (IRSN), Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP No. 17, F-92262 Fontenay-aux-Roses Cedex, France;2. Clermont Université, UMR CNRS 6247 and Centre de Recherche en Nutrition Humaine, 24, Avenue des Landais, F-63177 Aubière Cedex, France
Abstract:Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on contaminated grounds remains the main source for internal exposure to ionizing radiations, and primarily to cesium 137 (137Cs). Though the effects of a long-term internal contamination with radionuclides are poorly documented, several non-cancerous pathologies have been described in this population. However, lipid metabolism was never investigated after chronic internal contamination although disturbances were observed in externally-exposed people. In this regard, we assessed the effects of a chronic ingestion of 137Cs on hepatic and cerebral cholesterol metabolism. To mimic a chronically-exposed population, rats were given 137Cs-supplemented water at a post-accidental dose (150 Bq/rat/day) during 9 months. The plasma profile, and brain and liver cholesterol concentrations were unchanged. A decrease of ACAT 2, Apo E, and LXR < alpha > mRNA levels was recorded in the liver. In the brain, a decrease of CYP27A1 and ACAT 1 gene expression was observed. These results clearly show that cholesterol metabolism is not disrupted by a chronic ingestion of 137Cs, although several molecular alterations are observed. This work would be interestingly completed by studying the influence of 137Cs in models likely more sensitive to contaminants, such as the fetus or individuals susceptible to a lipidic disease.
Keywords:137Cs, Cesium 137   ABC, adenosine triphosphate binding cassette transporter   ACAT, acylCoenzymeA: cholesterol acyltransferase   ALT, alanine aminotransferase   Apo, apolipoprotein   AST, aspartate aminotransferase   CYP, cytochrome P450   FXR, farnesoid-X-receptor   GGT, gamma-glutamyltranspeptidase   HDL, high-density lipoprotein   HMGCoA R/S, 3-hydroxy-3-methylglutaryl Coenzyme A Reductase/Synthase   HPRT, hypoxanthine-guanine phosphoribosyltransferase   HNF, hepatocyte nuclear factor   LDL, low-density lipoprotein   LDLr, low-density lipoprotein receptor   LRH-1, liver receptor homolog-1   LXR, liver-X-receptor   PPAR, peroxisome proliferator-activated receptor   RXR, retinoid-X-receptor   SHP, small heterodimer partner   SR-B1, scavenger receptor class B type 1   SREBP, sterol regulatory element binding protein
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