title: Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.
abstract: Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car(+/+) and Car(-/-) mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car(+/+) females but not of Car(-/-) female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hours after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.
authors.affiliation: Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America. sueyoshi@niehs.nih.gov
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: William D
authors.initials: WD
authors.lastname: Green
authors.forename: Kellie
authors.initials: K
authors.lastname: Vinal
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Woodrum
authors.forename: Rick
authors.initials: R
authors.lastname: Moore
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000090702:Constitutive Androstane Receptor; D004967:Estrogens / Q000097:blood; D005737:Garlic / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013440:Sulfides / Q000494:pharmacology*; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: D000498:Allyl Compounds; D000090702:Constitutive Androstane Receptor; D004967:Estrogens; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D013440:Sulfides; C038491:allyl sulfide; D015238:Sulfotransferases; C020122:estrone sulfotransferase