Ah receptor-dependent CYP1A induction by two carotenoids, canthaxanthin and beta-apo-8'-carotenal, with no affinity for the TCDD binding site
Ah receptor-dependent CYP1A induction by two carotenoids, canthaxanthin and beta-apo-8'-carotenal, with no affinity for the TCDD binding site
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DOI：
10.1016/s0006-2952(97)00176-7
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发表时间：
1997-07-15
影响因子：
5.8
通讯作者：
Lesca, P
中科院分区：
文献类型：
--
作者：
Gradelet, S;Astorg, P;Lesca, P
对雄性C57BL/6小鼠（Ah受体应答型）、雄性DBA/2小鼠（Ah受体低应答型）和雌性Ah受体基因敲除小鼠的肝微体和细胞质进行了I期和II期外源代谢酶活性测定，并进行了CYP1A免疫印迹分析。这些小鼠饲喂含有300 mg/kg非维生素a原类胡萝卜素角黄素或维生素a原类胡萝卜素β -载脂蛋白8′-胡萝卜素的饲料14天。或者直接注射了3-甲基胆蒽。先前的研究表明，一些类胡萝卜素，如canehaxanthin和β -apo-8′-胡萝卜素，在给予大鼠时是肝脏CYP1A1和1A2的强诱导剂。在这项工作中，只有角黄素在C57BL/6小鼠中诱导了CYP1A1和1A2，而β -apo-8′-胡萝卜素在该菌株中仅诱导了CYP1A2。两种类胡萝卜素均未改变Ah受体CYP1A1/2蛋白含量或低响应DBA/2酶活性。或Ah受体基因敲除小鼠。将C57BL/6小鼠肝组织制备的细胞质与[H-3] 2,3,7,8-四氯二苯并-对苯二英（TCDD）在角黄素或β -载脂蛋白8′-胡萝卜素的存在下孵育，并通过蔗糖密度梯度沉淀法分析：即使大量过量存在，两种类胡萝卜素也不会与TCDD竞争C57BL/6小鼠胞质Ah受体的TCDD结合位点。简而言之，类胡萝卜素角黄素或β -载脂蛋白8′-胡萝卜素通过Ah受体依赖途径诱导小鼠Cypla基因，但不与Ah受体结合。(C) 1997爱思唯尔科学有限公司
The assays of several phase I and phase II xenobiotic-metabolizing enzyme activities, as well as CYP1A immunoblot analysis, were performed in liver microsomes and cytosol of male C57BL/6 mice (Ah receptor-responsive), of male DBA/2 mice (Ah receptor-low responsive) and of female Ah receptor gene knockout mice that were fed diets containing 300 mg/kg of a nonprovitamin A carotenoid, canthaxanthin, or a provitamin A carotenoid, beta-apo-8'-carotenal for 14 days, or which were injected i.p. with 3-methylcholanthrene. Previous studies have shown that some carotenoids, such as canehaxanthin and beta-apo-8'-carotenal, are strong inducers of liver CYP1A1 and 1A2 when given to rats. In this work, only canthaxanthin induced both CYP1A1 and 1A2 in C57BL/6 mice, whereas beta-apo-8'-carotenal induced only CYP1A2 in this strain. Neither of the two carotenoids modified CYP1A1/2 protein contents or enzyme activities in Ah receptor-low responsive DBA/2. or in Ah receptor gene knockout mice. Cytosol prepared from C57BL/6 mice liver tissue was incubated with [H-3] 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence of canthaxanthin or beta-apo-8'-carotenal and analyzed by sucrose density gradient sedimentation: neither of the carotenoids, even when present in large excess, competed with TCDD for the TCDD binding site of the cytosolic Ah receptor of C57BL/6 mice. In brief, the carotenoids canthaxanthin or beta-apo-8'-carotenal induced Cypla genes in mice through an Ah receptor-dependent pathway, but did not bind to the Ah receptor. (C) 1997 Elsevier Science Inc.