Expression of Constitutive Androstane Receptor Splice Variants in Rat Liver and Lung and Their Functional Properties(Molecular and Cell Biology)
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概要
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The mammalian constitutive androstane receptor (CAR) is a transcription factor that participates in controlling the expression of xenobiotic metabolizing and transporting genes in response to xenobiotics in an organ-specific manner. In addition to the wild-type CAR (CAR WT) mRNA, mRNAs for five splice variants (SVs) could be detected in the liver of 7-week-old male Wistar rats by RT-PCR using primer pairs covering a full-length mRNA derived from 9 exons; insertion of 18 bp at the 5'-end of intron 8 with or without deletion of 3 bp from the 5'-end of exon 7 (CAR SV1 or SV2), deletion of 4 bp from the 5'-end of exon 8 (CAR SV3), insertion of 195 bp intron 7 (CAR SV4), and insertion of 91 bp intron 6 (CAR SV5). In contrast, only CAR SV5 was detected in lung. Due to the introduction of novel stop codons, all the SVs were considered to code for premature proteins. The liver homogenate gave two protein bands in the vicinity of 37 kDa on Western blotting. They were attributable to CAR WT and SV-complex, respectively, based on their putative molecular weights in descending order. Upon cotransfection with the reporter plasmid, only the cells transfected with the CAR SV4-expression plasmid showed enhanced luciferase activity similar to the WT-transfected cells, for which the further splicing of the remaining intron 7 seemed to be responsible. The transactivation-defective SVs downregulated CAR WT-induced luciferase activity to some extent in the cotransfection experiments.
- 社団法人日本薬学会の論文
- 2005-11-01
著者
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Kanno Yuichiro
Faculty of Pharmaceutical Sciences, Toho University
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Inouye Yoshio
Faculty of Pharmaceutical Sciences, Toho University
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Mizuno Masaki
Department Of Environmental Health Faculty Of Pharmaceutical Sciences Toho University
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Mizuno Masaki
東邦大学 薬学部公衆衛生学
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Nakahama Takayuki
Fac. Of Pharmaceutical Sciences Toho Univ.
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Nakahama Takayuki
Faculty Of Pharmaceutical Sciences Toho University
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Nakahama Takayuki
Faculty Of Pharmuceutical Sciences Toho University
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Inouye Yoshio
Fac. Of Pharmaceutical Sciences Toho Univ.
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Inouye Yoshio
Faculty Of Pharmaceutical Sciences Toho University
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Inouye Yoshio
科学警察研究所
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Inouye Y
Faculty Of Pharmuceutical Sciences Toho University
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Kanno Yuichiro
Fac. Of Pharmaceutical Sciences Toho Univ.
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Kanno Yuichiro
Faculty Of Pharmaceutical Sciences Toho University
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Mori Emi
Faculty Of Pharmaceutical Sciences Toho University
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AOKI Sho
Faculty of Pharmaceutical Sciences, Toho University
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MOCHIZUKI Megumi
Faculty of Pharmaceutical Sciences, Toho University
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Nakahama Takayuki
Department Of Environmental Health Faculty Of Pharmaceutical Sciences Toho University
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Aoki Sho
Faculty Of Pharmaceutical Sciences Toho University
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Inouye Y
Faculty Of Pharmaceutical Sciences Toho University
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Mochizuki Megumi
Department Of Environmental Health Faculty Of Pharmaceutical Sciences Toho University
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