Involvement of nuclear factor-1 (NF1) binding motif in the regucalcin gene expression of rat kidney cortex: the expression is suppressed by cisplatin administration.
The binding of nuclear factor on the promoter region of the regucalcin gene and the expression of regucalcin in the kidney cortex of rats was investigated. Nuclear extracts from kidney cortex were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position -523 and -506 in the 5'-flanking region of the rat regucalcin gene, which contains a nuclear factor 1 (NF1) consensus motif TTGGC(N)6CC, competed with the probe for the binding of the nuclear protein from kidney cortex. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The binding of nuclear factor on the 5'-flanking region was clearly reduced in the kidney cortex obtained at 1, 2, and 3 days after a single intraperitoneal administration of cisplatin (1.0 mg/100 g body wt) to rats. Moreover, cisplatin administration caused a remarkable decrease in regucalcin mRNA levels and regucalcin concentration in the kidney cortex. Also, serum regucalcin concentration was significantly decreased by cisplatin administration. Meanwhile, serum urea nitrogen concentration was markedly elevated by cisplatin administration. The present study demonstrates that the specific nuclear factor binds to the NF1-like sequence in the promotor region of regucalcin gene in the kidney cortex of rats, and that the nuclear factor binding and regucalcin expression are suppressed by cisplatin administration.
Misawa
H
H
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
Yamaguchi
M
M
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases; D002945:Cisplatin / Q000494:pharmacology*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D051839:NFI Transcription Factors; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015238:Sulfotransferases; D013997:Time Factors; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051839:NFI Transcription Factors; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C486169:Ybx1 protein, rat; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D002265:Carboxylic Ester Hydrolases; C513325:Rgn protein, rat; D002945:Cisplatin