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Titolo:
HYPERRESPONSIVENESS OF VITAMIN-D-RECEPTOR GENE-EXPRESSION TO 1,25-DIHYDROXYVITAMIN-D-3 - A NEW CHARACTERISTIC OF GENETIC HYPERCALCIURIC STONE-FORMING RATS
Autore:
YAO JL; KATHPALIA P; BUSHINSKY DA; FAVUS MJ;
Indirizzi:
UNIV CHICAGO,PRITZKER SCH MED,DEPT MED,5841 S MARYLAND AVE CHICAGO IL60637 UNIV CHICAGO,PRITZKER SCH MED,DEPT MED CHICAGO IL 60637 UNIV ROCHESTER,SCH MED & DENT ROCHESTER NY 14642
Titolo Testata:
The Journal of clinical investigation
fascicolo: 10, volume: 101, anno: 1998,
pagine: 2223 - 2232
SICI:
0021-9738(1998)101:10<2223:HOVGT1>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-CALCIUM DIET; ABSORPTIVE HYPERCALCIURIA; IDIOPATHIC HYPERCALCIURIA; SERUM 1,25-DIHYDROXYVITAMIN-D; MOLECULAR-CLONING; UP-REGULATION; CALBINDIN-D28K; EXCRETION; INVIVO; ACID;
Keywords:
VITAMIN D RECEPTOR; GENE EXPRESSION; RAT; 1,25(OH)(2)D-3; HYPERCALCIURIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
J.L. Yao et al., "HYPERRESPONSIVENESS OF VITAMIN-D-RECEPTOR GENE-EXPRESSION TO 1,25-DIHYDROXYVITAMIN-D-3 - A NEW CHARACTERISTIC OF GENETIC HYPERCALCIURIC STONE-FORMING RATS", The Journal of clinical investigation, 101(10), 1998, pp. 2223-2232

Abstract

Hypercalciuria in genetic hypercalciuric stone-forming (GHS) rats is accompanied by intestinal Ca hyperabsorption with normal serum 1,25-dihydroxyvitamin D-3[1,25(OH)(2)D-3] levels, elevation of intestinal, kidney, and bone vitamin D receptor (VDR) content, and greater 1,25(OH)(2)D-3-induced bone resorption in vitro. To test the hypothesis that hyperresponsiveness of VDR gene expression to 1,25(OH)(2)D-3 may mediatethese observations, male GHS and wild-type Sprague-Dawley normocalciuric control rats were fed a normal Ca diet (0.6% Ca) and received a single intraperitoneal injection of either 1,25(OH)(2)D-3 (10-200 ng/100g body wt) or vehicle. Total RNAs were isolated from both duodenum and kidney cortex, and the VDR and calbindin mRNA levels were determinedby Northern blot hybridization using specific cDNA probes. Under basal conditions, VDR mRNA levels in GHS rats were lower in duodenum and higher in kidney compared with wild-type controls. Administration of 1,25(OH)2D(3) increased VDR gene expression significantly in GHS but notnormocalciuric animals, in a time- and dose-dependent manner. In vivohalf-life of VDR mRNA wall similar in GHS and control rats in both duodenum and kidney, and was prolonged significantly (from 4-5 to > 8 h)by 1,25(OH)(2)D-3 administration. Neither inhibition of gene transcription by actinomycin D nor inhibition of de novo protein synthesis with cycloheximide blocked the upregulation of VDR gene expression stimulated by 1,25(OH)(2)D-3 administration. No alteration or mutation was detected in the sequence of duodenal VDR mRNA from GHS rats compared with wild-type animals. Furthermore, 1,25(OH)(2)D-3 administration also led to an increase in duodenal and renal calbindin mRNA levels in GHS rats, whereas they were either suppressed or unchanged in wild-type animals. The results suggest that GHS rats hyperrespond to minimal dosesof 1,25(OH)(2)D-3 by an upregulation of VDR gene expression. This hyperresponsiveness of GHS rats to 1,25(OH)(2)D-3 (a) occurs through an increase in VDR mRNA stability without involving alteration in gene transcription, de novo protein synthesis, or mRNA sequence; and (b) is likely of functional significance, and affects VDR-responsive genes in 1,25(OH)(2)D-3 target tissues. This unique characteristic suggests thatGHS rats may be susceptible to minimal fluctuations in serum 1,25(OH)(2)D-3, resulting in increased VDR and VDR-responsive events, which inturn may pathologically amplify the actions of 1,25(OH)(2)D-3 on Ca metabolism that thus contribute to the hypercalciuria and stone formation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 17:00:57