Transcriptional Profile of CYP3As and Functional Expression of CYP3A29 from Piglets

摘要

Expression profile of CYP3A individuals from piglets and characterization of CYP3A29 were investigated. Real-Time PCR showed that the liver and small intestines present the highest expression levels of CYP3A29, a human CYP3A4 homolog. The CYP3A29 was functional expressed in Bac-to-Bac baculovirus expression system together with NADPH p450 reductase (NPR) and cytochrome b5. For nifedipine oxidation (NOD) activity, recombinant CYP3A29 system showed similar enzyme kinetic parameters (Km = 14.1 ~ 25.3 muM) to human recombinant CYP3A4, and a little variant to liver microsomes (Km = 29.6 ~ 45.2 muM) from piglets. The NOD activity of recombinant CYP3A29 was strongly inhibited by ketoconazole (KET) and troleandomycin (TAO), and was slightly changed by inhibitors for other p450 enzymes from human. These results provided in detailed information of the characterizations of CYP3A29. We conclude from these results that caution should be hold when specific inhibitors or probes for human p450 enzymes are employed to investigate the veterinary drug metabolism.