Selective Centrilobular Expression of the Aryl Hydrocarbon Receptor in Rat Liver

作者: Magnus Ingelman-Sundberg , Kai O. Lindros , Teija Oinonen , Inger Johansson

DOI:

关键词:

摘要: The aryl hydrocarbon receptor (AHR) is a transcriptional activator of genes encoding group drug-metabolizing enzymes, including cytochrome P450 1A1 ( CYP1A1 ), glutathione S -transferase, tumor-associated aldehyde dehydrogenase and quinone reductase. Both the constitutive inducible expression these in liver zonated, i.e. , dominant hepatocytes centrilobular region, poorly understood position-dependent phenomenon. By comparing cell lysates obtained from opposite acinar regions we observed that immunoreactive AHR protein was almost exclusively confined to cells. mRNA, as analyzed by reverse transcriptase polymerase chain reaction, exhibited similar, although somewhat less pronounced zonation. contrast, only slight zonation nuclear translocator mRNA observed. Treatment rats with omeprazole, an atypical nonligand AHR, caused zone-specific induction region similar seen after pretreatment ligand 3-methylcholanthrene. Our results suggest zone-restricted will allow AHR-regulated but limit their periportal region.

参考文章(34)
Dominique Diaz, Isabelle Fabrev, Martine Daujat, Bernard Saint Aubert, Philippe Bories, Henri Michel, Patrick Maurel, Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450 Gastroenterology. ,vol. 99, pp. 737- 747 ,(1990) , 10.1016/0016-5085(90)90963-2
T Oinonen, K O Lindros, Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver Biochemical Journal. ,vol. 309, pp. 55- 61 ,(1995) , 10.1042/BJ3090055
H. Okayama, M. Kawaichi, M. Brownstein, F. Lee, T. Yokota, K. Arai, [1] High-efficiency cloning of full-length cDNA; Construction and screening of cDNA expression libraries for mammalian cells Methods in Enzymology. ,vol. 154, pp. 3- 28 ,(1987) , 10.1016/0076-6879(87)54067-8
C.M. Sadek, B.L. Allen-Hoffmann, Cytochrome P450IA1 is rapidly induced in normal human keratinocytes in the absence of xenobiotics. Journal of Biological Chemistry. ,vol. 269, pp. 16067- 16074 ,(1994) , 10.1016/S0021-9258(17)33974-1
Chantal Gleizes, Claudine Eeckhoutte, Thierry Pineau, Michel Alvinerie, Pierre Galtier, Inducing effect of oxfendazole on cytochrome P450IA2 in rabbit liver: Consequences on cytochrome P450 dependent monooxygenases Biochemical Pharmacology. ,vol. 41, pp. 1813- 1820 ,(1991) , 10.1016/0006-2952(91)90119-P
C.M. Sadek, B.L. Allen-Hoffmann, Suspension-mediated induction of Hepa 1c1c7 Cyp1a-1 expression is dependent on the Ah receptor signal transduction pathway. Journal of Biological Chemistry. ,vol. 269, pp. 31505- 31509 ,(1994) , 10.1016/S0021-9258(18)31723-X
W.Michael McDonnell, James M. Scheiman, Peter G. Traber, Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract. Gastroenterology. ,vol. 103, pp. 1509- 1516 ,(1992) , 10.1016/0016-5085(92)91171-Y
M. Ingelman-Sundberg, F. Sjoqvist, L. Bertilsson, I. Johansson, Qun-Ying Yue, M. Oscarson, Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Molecular Pharmacology. ,vol. 46, pp. 452- 459 ,(1994)
J. Takahashi, Circadian clock genes are ticking Science. ,vol. 258, pp. 238- 240 ,(1992) , 10.1126/SCIENCE.1384127