tailieunhanh - Báo cáo khoa học: 17b-Hydroxysteroid dehydrogenase type 11 is a major peroxisome proliferator-activated receptor a-regulated gene in mouse intestine

In order to study the role of peroxisome proliferator-acti-vated receptor ain mouse intestine, its agonist-induced proteins were identified by peptide mass fingerprinting fol-lowed byNorthern blot analysis using their cDNAs. One of the most remarkably induced proteins was identified as 17b-hydroxysterol dehydrogenase type 11. Its very rapid induction by various agonists was most efficient in intestine and then in liver. These findings together with recently reported results showing the enzyme family’s wide substrate spectrum, including not only glucocorticoids and sex ster-oidsbut alsobileacids, fattyacidsandbranchedchainamino acids,. | Eur. J. Biochem. 271 4141-4146 2004 FEBS 2004 doi 17b-Hydroxysteroid dehydrogenase type 11 is a major peroxisome proliferator-activated receptor a-regulated gene in mouse intestine Kiyoto Motojima Department of Biochemistry Meiji Pharmaceutical University Kiyose Tokyo Japan In order to study the role of peroxisome proliferator-acti-vated receptor a in mouse intestine its agonist-induced proteins were identified by peptide mass fingerprinting followed by Northern blot analysis using their cDNAs. One of the most remarkably induced proteins was identified as 17p-hydroxysterol dehydrogenase type 11. Its very rapid induction by various agonists was most efficient in intestine and then in liver. These findings together with recently reported results showing the enzyme family s wide substrate spectrum including not only glucocorticoids and sex steroids but also bile acids fatty acids and branched chain amino acids suggest new roles for both peroxisome proliferator-activated receptor a and 17b-hydroxysterol dehydrogenase type 11 in lipid metabolism and or detoxification in the intestine. Keywords PPAR intestine hydroxysteroid dehydrogenase lipid metabolism. Peroxisome proliferator-activated receptors PPARa P ỗ and c are members of the nuclear hormone receptor superfamily and function as ligand-dependent transcription factors playing crucial roles in several processes including energy metabolism cellular differentiation and inflammation 1 2 . It is now well accepted that PPARa is particularly important in lipid catabolism in the liver by upregulating the expression of a variety of genes that encode proteins involved in fatty acid transport 3 a-oxidation and lipoprotein metabolism 4 5 . However it is important to point out that these studies have been mostly carried out using rodent models and strong synthetic PPARa agonists. PPARa was originally cloned from a mouse cDNA library to explain a rodent-specific response called peroxisome .