An ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes aflatoxin B1 defines a subfamily of aldo-keto reductases

E. M. Ellis, D. J. Judah, G. E. Neal, J. D. Hayes

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    119 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)10350-10354
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume90
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 1993

    Keywords

    • Aflatoxin B1/metabolism
    • Aldehyde Reductase/biosynthesis
    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • DNA Primers
    • DNA, Complementary/isolation & purification
    • Enzyme Induction
    • Ethoxyquin/pharmacology
    • Humans
    • Kinetics
    • Liver/drug effects
    • Male
    • Molecular Sequence Data
    • Open Reading Frames
    • Plasmids
    • Polymerase Chain Reaction/methods
    • RNA, Messenger/biosynthesis
    • Rats
    • Rats, Inbred F344
    • Restriction Mapping
    • Sequence Homology, Amino Acid

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