CYTOCHROMES-P-450 IN HUMAN HEPATOCYTE PLASMA-MEMBRANE - RECOGNITION BY SEVERAL AUTOANTIBODIES

被引:133
作者
LOEPER, J
DESCATOIRE, V
MAURICE, M
BEAUNE, P
BELGHITI, J
HOUSSIN, D
BALLET, F
FELDMANN, G
GUENGERICH, FP
PESSAYRE, D
机构
[1] HOP BEAUJON,CHIRURG KLIN,INSERM,U24,F-92118 CLICHY,FRANCE
[2] INSERM,U24,CLICHY,FRANCE
[3] INSERM,U327,F-75005 PARIS,FRANCE
[4] INSERM,U75,F-75005 PARIS,FRANCE
[5] INSERM,U181,F-75005 PARIS,FRANCE
[6] HOP ST ANTOINE,F-75571 PARIS 12,FRANCE
[7] HOP COCHIN,CHIRURG KLIN,F-75674 PARIS 14,FRANCE
[8] VANDERBILT UNIV,DEPT BIOCHEM,NASHVILLE,TN 37240
[9] VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37240
关键词
D O I
10.1016/0016-5085(93)90853-5
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Anti-cytochrome P-450 autoantibodies are present in several forms of autoimmune hepatitis. The possibility that cytochromes P-450 are present in the plasma membrane of human hepatocytes was examined. Methods: (1) Plasma membranes with microsomal contamination < 1%, as judged from the activities of glucose-6-phosphatase and NADH-cytochrome c reductase, were prepared. (2) After exposure of uncut, fixed hepatocytes to antibodies, immunofluorescence and immunoperoxidase studies were performed. Results: (1) The specific content of cytochrome P-450 in plasma membrane was 9% of that in microsomes. Plasma membranes showed NADPH-cytochrome c reductase and mono-oxygenase activities; immunoblots showed the presence of cytochromes P-450 1A2, 2C, 2D6, 2E1, and 3A4; cytochromes P-450 1A2, 2D6, and 2C were also recognized by antiliver microsome and anti-liver/kidney microsome type 1 and type 2 autoantibodies, respectively. (2) Immunofluorescence and immunoperoxidase labeling of the plasma membrane was observed with the three autoantibodies and with anti-cytochrome P-450 1A2, 2C, 2E1, or 3A4. Conclusions: It is concluded that cytochromes P-450 are present and functional in the plasma membrane of human hepatocytes and that anti-cytochrome P-450 autoantibodies recognize epitopes expressed on the outer surface. © 1993.
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页码:203 / 216
页数:14
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