title: Expression and regulation of the sterol half-transporter genes ABCG5 and ABCG8 in rats.
abstract: The ABCG5 and ABCG8 genes encode half-transporter proteins that heterodimerize to form a transporter of plant sterols and cholesterol. The purpose of this study was to examine the expression and regulation of ABCG5 and ABCG8 at the mRNA level in Sprague-Dawley rats. Both ABCG5 and ABCG8 mRNA were expressed primarily in rat small intestine and liver, and gender-specific differences in expression were observed. The effects of treatment with a battery of microsomal enzyme inducers on ABCG5 and ABCG8 mRNA were examined; most treatments had no effect, but of three PXR ligands, PCN was an effective inducer, spironolactone was repressive, and dexamethasone was ineffective. The effects of a 1% cholesterol diet on the regulation of rat ABCG5 and ABCG8 were also examined, and compared with those in C57BL/6 mice. Cholesterol caused a suppression of ABCG5 and ABCG8 mRNA in rat liver, but the same treatment increased the expression of these genes in mouse liver. ABCG5 and ABCG8 mRNA was also induced by cholesterol in rat ileum, but not mouse ileum. These results suggest variation between rats and mice in regulatory mechanisms controlling ABCG5 and ABCG8 expression, and may explain some differences in lipid metabolism observed between these two species.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Dieter
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Maher
authors.forename: Xingguo
authors.initials: X
authors.lastname: Cheng
authors.forename: Curtis D
authors.initials: CD
authors.lastname: Klaassen
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; C480692:Abcg5 protein, rat; C480693:Abcg8 protein, rat; D008074:Lipoproteins; D012333:RNA, Messenger; D015262:Xenobiotics; D002784:Cholesterol