Enriched uranium affects the expression of vitamin D receptor and retinoid X receptor in rat kidney
Résumé
An increasing awareness of the radiological impact of the nuclear power industry and other nuclear technologies is observed nowadays on general population. This led to renew interest to assess the health impact of the use of enriched uranium (EU). The aim of this work was to investigate in vivo the effects of a chronic exposure to EU on vitamin D3 metabolism, a hormone essential in mineral and bone homeostasis. Rats were exposed to EU in their drinking water for 9 months at a concentration of 40 mg l-1 (1 mg/rat day). The contamination did not change vitamin D plasma level. Vitamin D receptor (vdr) and retinoid X receptor alpha (rxrα), encoding nuclear receptors involved in the biological activities of vitamin D, showed a lower expression in kidney, while their protein levels were paradoxically increased. Gene expression of vitamin D target genes, epithelial Ca2+ channel 1 (ecac1) and Calbindin-D28k (cabp-d28k), involved in renal calcium transport were decreased. Among the vitamin D target organs examined, these molecular modifications occurred exclusively in the kidney, which confirms that this organ is highly sensitive to uranium exposure. In conclusion, this study showed that a chronic exposure to EU affects both mRNA and protein expressions of renal nuclear receptors involved in vitamin D metabolism, without any modification of the circulating vitamin D. © 2008 Elsevier Ltd. All rights reserved.
Mots clés
calbindin
calcium
cell nucleus receptor
colecalciferol
messenger RNA
retinoid X receptor alpha
uranium
vanilloid receptor 5
vitamin D receptor
animal experiment
animal tissue
article
biological activity
brain
calcium blood level
calcium transport
controlled study
enzyme activity
gene sequence
homeostasis
in vivo study
intestine absorption
kidney
kidney tubule absorption
long term exposure
male
nonhuman
nucleotide sequence
polymerase chain reaction
protein blood level
protein expression
rat
vitamin blood level
vitamin D metabolism
water contamination
Western blotting
Animals
Brain
Dose-Response Relationship
Drug
Drug Evaluation
Preclinical
Duodenum
Gene Expression Regulation
Kidney
Male
Rats
Sprague-Dawley
Receptors
Calcitriol
Retinoid X Receptors
RNA
Messenger
Uranium
Vitamin D
Rattus