國家衛生研究院 NHRI:Item 3990099045/1120

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Title:	Effects of xenobiotics and peroxisome proliferator-activated receptor-alpha on the human UDPglucose dehydrogenase gene expression
Authors:	Vatsyayan, J;Lee, SJ;Chang, HY
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	During drug metabolism, UDPglucuronate, a product of the reaction catalyzed by the enzyme UDPglucose dehydrogenase (UGDH), is conjugated with the metabolites to facilitate their elimination. So far, it is not known whether xenobiotics can modulate the UGDH gene expression. This question was tested by treating the human hepatoma cells HepG2 with several medicinal compounds and the UGDH gene expression analyzed by using real-time PCR. Both eugenol and rifampicin showed activation of the gene expression. Piperine showed slight downregulation of the UGDH gene expression, whereas no effect was observed with acetaminophen treatment. Through promoter-reporter gene assays, we found that rifampicin showed multiple-folds activation of a 1.23-kb UGDH promoter construct, and the region likely to respond to rifampicin treatment is located within the range -632 to -1050. A bioinformatics search for xenobiotic response element in this region has predicted a binding motif for the peroxisome proliferator-activated receptor-alpha(PPAR alpha) at position -1003. A mutation at the predicted PPAR recognizing motif eliminated normal suppression as well as the rifampicin activation effect on the UGDH promoter activity. Cotransfection with the PPAR alpha and retinoid X receptor-alpha expression vectors and subsequent treatment with the PPAR alpha agonist led to the suppression of the UGDH promoter activity either in the presence or absence of rifampicin. Our study, for the first time, shows the UGDH gene to be under xenobiotic regulation and delineates a motif responsible for rifampicin response and transcriptional repression of the UGDH gene.
Keywords:	Biochemistry & Molecular Biology;Toxicology
Date:	2005
Relation:	Journal of Biochemical and Molecular Toxicology. 2005;19(5):279-288.
Link to:	http://dx.doi.org/10.1002/jbt.20099
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1095-6670&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000233326400001
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=27844436635
Appears in Collections:	[Shiow-Ju Lee] Periodical Articles

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