Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: Induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer
Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: Induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer
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DOI：
10.1016/j.fct.2011.03.009
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发表时间：
2011-06-01
影响因子：
4.3
通讯作者：
Ishizuka, Mayumi
中科院分区：
文献类型：
--
作者：
Ohno, Marumi;Darwish, Wageh S.;Ishizuka, Mayumi
虾青素（Axanthin，Ax）是一种叶黄素类胡萝卜素，具有细胞色素P450（CYP）1A依赖性活性。CYP 1A是最重要的酶之一参与阶段！它能促进化学物质的代谢，并能激活各种诱变剂。为了研究Ax对一种典型的前诱变剂苯并[a]芘通过CYP 1A代谢活化的影响，我们对雄性Wistar大鼠口服含Ax的油（100 mg Ax/kg体重/天，连续3天）。在处理的大鼠肝脏中，CYP 1A 1 mRNA、蛋白质及其活性的表达显著增加（分别为5.5倍、8.5倍和2.5倍）。与此相反，第二阶段酶（谷胱甘肽S-转移酶和葡萄糖醛酸转移酶）的活动没有调制的AX含油。因此，在艾姆斯试验中，与对照组相比，Ax-treated大鼠中苯并[a]芘的致突变性更强。另一方面，给药组肝微粒体中NADPH P450还原酶活性降低。这一结果表明，Ax可能抑制了CYP 1A催化活性所必需的电子供应，并间接降低了CYP 1A活性。总之，摄入含Ax的油可通过两种不同的机制改变CYP 1A依赖性活性：（1）诱导CYP 1A 1 mRNA、蛋白表达和活性;（2）抑制酶的电子供应。(C)2011爱思唯尔有限公司版权所有。
Astaxanthin (Ax), a xanthophyll carotenoid, is reported to induce cytochrome P450 (CYP) 1A-dependent activity. CYP1A is one of the most important enzymes participating in phase! metabolism for chemicals, and it can activate various mutagens. To investigate the effect of Ax on the metabolic activation of a typical promutagen, benzo[a]pyrene by CYP1A, we orally administrated Ax-containing oil (100 mg Ax/kg body weight/day for 3 days) to male Wistar rats. In the treated rat liver, expression of CYP1A1 mRNA, protein, and its activity were significantly increased (5.5-, 8.5-, and 2.5-fold, respectively). In contrast, the activities of phase II enzymes (glutathione S-transferase and glucuronosyl-transferase) were not modulated by Ax-containing oil. As a consequence, the mutagenicity of benzo[a]pyrene was more enhanced in Ax-treated rats, compared with controls in the Ames assay. On the other hand, NADPH P450 reductase activity was decreased in liver microsomes from the treated group. This result suggests the possibility that Ax inhibits the electron supply necessary for CYP catalytic activities and decreases CYP1A activity indirectly. In conclusion, Ax-containing oil intake can alter CYP1A-dependent activities through two different mechanisms: (1) induction of CYP1A1 mRNA, protein expression, and activity; and (2) inhibition of the electron supply for the enzyme. (C) 2011 Elsevier Ltd. All rights reserved.