Modifications of the expression of genes involved in cerebral cholesterol metabolism in the rat following chronic ingestion of depleted uranium
Résumé
Depleted uranium results from the enrichment of natural uranium for energetic purpose. Its potential dispersion in the environment would set human populations at risk of being contaminated through ingestion. Uranium can build up in the brain and induce behavior disorders. As a major constituent of the myelin sheath, cholesterol is essential to brain function, and several neurological pathologies result from a disruption of cholesterol metabolism. To assess the effect of a chronic contamination with depleted uranium on cerebral cholesterol metabolism, rats were exposed to depleted uranium for 9 months through drinking water at 40 mg/l. The study focuses on gene expression. Cholesterol-catabolizing enzyme CYP46A1 displayed a 39% increase of its messenger RNA (mRNA) level. 3-Hydroxy-3-methylglutamyl CoA synthase gene expression rose from 91%. Concerning cholesterol transport, mRNA levels of scavenger receptor-B1 and adenosine triphosphate-binding cassette transporter A1 increased by 34% and that of apolipoprotein E by 75%. Concerning regulation, gene expression of nuclear receptors peroxisome proliferator-activated receptors α and γ increased by 46% and 36% respectively, whereas that of retinoid-X-receptor decreased by 29%. In conclusion, a chronic internal contamination with depleted uranium does not affect the health status of rats but induces molecular changes in the dynamic equilibrium of the cerebral cholesterol pool. Copyright © Humana Press 2008.
Mots clés
Hydroxymethylglutaryl-CoA Synthase
Male
Rats
Sprague-Dawley
Receptors
LDL
Scavenger Receptors
Class B
Steroid Hydroxylases
Transcription Factors
Uranium
apolipoprotein E
cholesterol 24 hydroxylase
drinking water
messenger RNA
oxygenase
peroxisome proliferator activated receptor alpha
peroxisome proliferator activated receptor gamma
retinoid X receptor
scavenger receptor
scavenger receptor BI
unclassified drug
uranium
ABC transporter
acyl coenzyme A
cholestanetriol 26 monooxygenase
cholesterol
cholesterol 24-hydroxylase
hydroxymethylglutaryl coenzyme A synthase
low density lipoprotein receptor
scavenger receptor B
steroid monooxygenase
transcription factor
3 hydroxy 3 methylglutamyl CoA synthase gene
animal experiment
article
brain metabolism
cholesterol metabolism
cholesterol synthesis
cholesterol transport
controlled study
gene
gene expression
gene expression regulation
intoxication
male
nonhuman
nucleotide sequence
rat
uranium intoxication
animal
brain cortex
drug effect
genetics
human
metabolism
physiology
Sprague Dawley rat
Rattus
Acyl Coenzyme A
Animals
ATP-Binding Cassette Transporters
Cerebral Cortex
Cholesterol
Cytochrome P-450 CYP27A1
Gene Expression Regulation
Enzymologic
Humans