An ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes aflatoxin B1 defines a subfamily of aldo-keto reductases
| Autor: | David J. Judah, Elizabeth M. Ellis, Gordon E. Neal, John D. Hayes |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
7-Dehydrocholesterol reductase Aflatoxin B1 DNA Complementary Molecular Sequence Data Restriction Mapping Reductase Polymerase Chain Reaction Open Reading Frames chemistry.chemical_compound Ethoxyquin Aldehyde Reductase Complementary DNA Animals Humans Amino Acid Sequence RNA Messenger Enzyme inducer DNA Primers chemistry.chemical_classification Aldo-keto reductase Multidisciplinary Base Sequence Sequence Homology Amino Acid biology Molecular biology Rats Inbred F344 Rats Kinetics Enzyme Liver chemistry Biochemistry Enzyme Induction biology.protein Research Article Plasmids |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:10350-10354 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.21.10350 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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