title: Differential gene expression of CYP3A isoforms in equine liver and intestines.
abstract: Recently, seven CYP3A isoforms - CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP129 - have been isolated from the horse genome. In this study, we have examined the hepatic and intestinal gene expression of these CYP3A isoforms using TaqMan probes. We have also studied the enzyme activity using luciferin-isopropyl acetal (LIPA) as a substrate. The results show a differential gene expression of the CYP3A isoforms in the liver and intestines in horses. In the liver, CYP3A89, CYP3A94, CYP3A96 and CYP3A97 were highly expressed, while in the intestine there were only two dominating isoforms, CYP3A93 and CYP3A96. The isoform CYP3A129 was not detected in the liver or the intestine, although this gene consists of a complete set of exons and should therefore code for a functional protein. It is possible that this gene is expressed in tissues other than the liver and intestines. In the intestine, both CYP3A96 and CYP3A93 showed the highest gene expression in the duodenum and the proximal parts of the jejunum. This correlated with a high protein expression in these tissues. Studies of the enzyme activity showed the same K(m) for the LIPA substrate in the liver and the intestine, while the maximum velocity (V(max)) in the liver was higher than in the intestine. Our finding of a differential gene expression of the CYP3A isoforms in the liver and the intestines contributes to a better understanding of drug metabolism in horses.
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden. eva.tyden@slu.se
authors.forename: E
authors.initials: E
authors.lastname: Tydén
authors.forename: M
authors.initials: M
authors.lastname: Löfgren
authors.forename: S
authors.initials: S
authors.lastname: Pegolo
authors.forename: F
authors.initials: F
authors.lastname: Capolongo
authors.forename: H
authors.initials: H
authors.lastname: Tjälve
authors.forename: P
authors.initials: P
authors.lastname: Larsson
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006736:Horses / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008861:Microsomes; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D051544:Cytochrome P-450 CYP3A