TAILIEUCHUNG - Báo cáo khoa học: Peroxisome proliferator-activated receptor a plays a vital role in inducing a detoxification system against plant compounds with crosstalk with other xenobiotic nuclear receptors

Peroxisome proliferator-activated receptora(PPARa) is thought to play an important role in lipid metabolism in the liver. To clarify the extra-hepatic and⁄or unknown function of PPARa, we previously performed a proteome analysis of the intestinal proteins and identified 17b-hydroxyster- | iFEBS Journal Peroxisome proliferator-activated receptor a plays a vital role in inducing a detoxification system against plant compounds with crosstalk with other xenobiotic nuclear receptors Kiyoto Motojima and Toshitake Hirai Department of Biochemistry Meiji PharmaceuticalUniversity Kiyose Tokyo Japan Keywords Detoxification drug-drug interaction PPAR P450 xenobiotic nuclear receptor Correspondence K. Motojima Department of Biochemistry Meiji PharmaceuticalUniversity 2-522-1 Noshio Kiyose Tokyo 204-8588 Japan Tel. Fax 81 424 95 8474 E-mail motojima@ Received 11 August 2005 revised 8 November 2005 accepted 14 November 2005 doi Peroxisome proliferator-activated receptor a PPARa is thought to play an important role in lipid metabolism in the liver. To clarify the extrahepatic and or unknown function of PPARa we previously performed a proteome analysis of the intestinal proteins and identified np-hydroxyster-oid dehydrogenase type 11 as a mostly induced protein by a PPARa ligand Motojima K. 2004 Eur. J. Biochem. 271 4141-4146 . Because of its supposed wide substrate specificity we examined the possibility that PPARa plays an important role in inducing detoxification systems for some natural foods by feeding mice with various plant seeds and grains. Feeding with sesame but not others often killed PPARa knockout mice but not wild-type mice. A microarray analysis of the sesame-induced mRNAs in the intestine revealed that PPARa plays a vital role in inducing various xenobiotic metabolizing enzymes in the mouse intestine and liver. A PPARa ligand alone could not induce most of these enzymes suggesting that there is an essential crosstalk among PPARa and other xenobiotic nuclear receptors to induce a detoxification system for plant compounds. According to the generally accepted view peroxisome proliferator-activated receptor a PPARa plays an important role in lipid catabolism in the liver 1 . However this view has been .

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