Antibodies to liver/kidney microsome1 in chronic active hepatitis recognize specific forms of hepatic cytochrome P-450.

Antibodies to liver/kidney microsome1 in chronic active hepatitis recognize specific forms of hepatic cytochrome P-450.
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慢性活动性肝炎中的肝/肾微粒体1抗体可识别特定形式的肝细胞色素 P-450。

DOI:
10.1016/0016-5085(88)90368-x
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发表时间:
1988
期刊:
影响因子:
29.4
通讯作者:
Alvarez,F
Alvarez,F
中科院分区:
医学1区
文献类型:
--
作者:
Waxman,DJ;Lapenson,DP;Krishnan,M;Bernard,O;Kreibich,G;Alvarez,F

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研究了慢性活动性肝炎儿童的抗肝/肾微粒体1阳性血清,以确定在这种自身免疫性疾病的诱导和进展过程中选择的微粒体抗原。用抗肝/肾微粒体1阳性血清对十二烷基硫酸钠凝胶溶解的人和大鼠肝脏微粒体蛋白进行免疫印迹分析,发现单个多肽为48千道尔顿(人微粒体)或50千道尔顿(大鼠微粒体)。50千道尔顿大鼠微粒体多肽水平在体内被几种已知可调节肝细胞色素P-450个体形式(酶)表达的药物抑制,其中苯巴比妥影响最大。在非变性条件下,对10个电泳均匀的大鼠肝细胞色素P-450型进行斑点斑点分析,发现两种甲基胆碱诱导型P-450 BNF-B和P-450 ISF-G (P-450基因亚家族IA)可被抗肝/肾微粒体抗体选择性识别。这些发现表明,与自身免疫性(抗肝/肾微粒体1)慢性活动性肝炎相关的血清与选择的大鼠肝脏P-450形式特异性反应,并表明这些自身抗体可能主要针对相应的人肝细胞色素的一种或多种组成形式。
Anti-liver/kidney microsome1-positive sera from children with chronic active hepatitis were studied in an effort to identify the microsomal antigens selected during induction and progression of this autoimmune disease. Immunoblot analysis of sodium dodecyl sulfate gel-resolved microsomal proteins from human and rat liver using anti-liver/ kidney microsome1-positive sera revealed a single polypeptide of 48 kilodaltons (human microsomes) or 50 kilodaltons (rat microsomes). Levels of the 50-kilodalton rat microsomal polypeptide were suppressed in vivo by several drugs known to modulate expression of individual forms (enzymes) of hepatic cytochrome P-450, with the largest decrease effected by phenobarbital. Dot blot analysis using a panel of 10 electrophoretically homogeneous rat liver cytochrome P-450 forms under nondenaturing conditions established that the two methylcholanthrene-inducible forms, P-450 BNF-B and P-450 ISF-G (P-450 gene subfamily IA), are selectively recognized by the anti-liver/kidney microsome1antibodies. These findings demonstrate that sera associated with autoimmune (anti-liver/kidney microsome1) chronic active hepatitis are specifically reactive with select rat hepatic P-450 forms and suggest that these autoantibodies may be principally directed against one or more constitutive forms of the corresponding human liver cytochromes.
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