Enriched uranium affects the expression of vitamin D receptor and retinoid X receptor in rat kidney.
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 D(3) 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) (1mg/rat day). The contamination did not change vitamin D plasma level. Vitamin D receptor (vdr) and retinoid X receptor alpha (rxralpha), 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 Ca(2+) 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.
Tissandié
E
E
Institute for Radiological protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP no.17, Fontenay-aux-Roses CEDEX, France.
Guéguen
Y
Y
Lobaccaro
J M A
JM
Grandcolas
L
L
Aigueperse
J
J
Gourmelon
P
P
Souidi
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics* / Q000378:metabolism; D014501:Uranium / Q000633:toxicity*; D014807:Vitamin D / Q000097:blood / Q000378:metabolism
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014807:Vitamin D; D014501:Uranium