Ellis E M, Judah D J, Neal G E, Hayes J D
Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, United Kingdom.
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10350-4. doi: 10.1073/pnas.90.21.10350.
Protection of liver against the toxic and carcinogenic effects of aflatoxin B1 (AFB1) can be achieved through the induction of detoxification enzymes by chemoprotectors such as the phenolic antioxidant ethoxyquin. We have cloned and sequenced a cDNA encoding an aldehyde reductase (AFB1-AR), which is expressed in rat liver in response to dietary ethoxyquin. Expression of the cDNA in Escherichia coli and purification of the recombinant enzyme reveals that the protein exhibits aldehyde reductase activity and is capable of converting the protein-binding dialdehyde form of AFB1-dihydrodiol to the nonbinding dialcohol metabolite. We show that the mRNA encoding this enzyme is markedly elevated in the liver of rats fed an ethoxyquin-containing diet, correlating with acquisition of resistance to AFB1. AFB1-AR represents the only carcinogen-metabolizing aldehyde reductase identified to date that is induced by a chemoprotector. Alignment of the amino acid sequence of AFB1-AR with other known and putative aldehyde reductases shows that it defines a subfamily within the aldo-keto reductase superfamily.
通过化学保护剂（如酚类抗氧化剂乙氧喹）诱导解毒酶，可以实现肝脏对黄曲霉毒素B1（AFB1）的毒性和致癌作用的保护。我们已经克隆并测序了一个编码醛还原酶（AFB1-AR）的cDNA，该酶在大鼠肝脏中因膳食乙氧喹而表达。该cDNA在大肠杆菌中的表达以及重组酶的纯化表明，该蛋白具有醛还原酶活性，并且能够将AFB1-二氢二醇的蛋白结合二醛形式转化为非结合二醇代谢物。我们表明，在喂食含乙氧喹饮食的大鼠肝脏中，编码该酶的mRNA显著升高，这与对AFB1抗性的获得相关。AFB1-AR是迄今为止鉴定出的唯一一种由化学保护剂诱导的致癌物代谢醛还原酶。AFB1-AR的氨基酸序列与其他已知和推定的醛还原酶的比对表明，它在醛酮还原酶超家族中定义了一个亚家族。
