期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 464, 期 2, 页码 241-250出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2007.04.024
关键词
lipid aldehydes; prostaglandins; retinals; steroid hormones; polycyclic aromatic hydrocarbons; anti-oxidant response element; reactive oxygen species
资金
- NCI NIH HHS [R01 CA090744, P01 CA092537-05, R01 CA090744-06A1, R01 CA039504-22, P01 CA092537, R01 CA039504, R01-CA39504-22, R01-CA90744-05, P01-CA92537-01A1] Funding Source: Medline
- NIDDK NIH HHS [R01 DK047015-13, R01-DK47015-13, R01 DK047015] Funding Source: Medline
- NIEHS NIH HHS [P30 ES013508-02, P30 ES013508-01A1, P30 ES013508] Funding Source: Medline
Aldo-keto reductases (AKRs) are a superfamily of NAD(P)H linked oxidoreductases that are generally monomeric 34-37 kDa proteins present in all phyla. The superfamily consists of 15 families, which contains 151 members (www.med.upenn.edu/akr). Thirteen human AKRs exist that use endogenous substrates (sugar and lipid aldehydes, prostaglandins, retinals and steroid hormones), and in many instances they regulate nuclear receptor signaling. Exogenous substrates include metabolites implicated in chemical carcinogenesis: NNK (4-(methylnitrosamino)-1-(3-pyridyl) 1-butanone), polycyclic aromatic hydrocarbon trans-dihydrodiols, and aflatoxin dialdehyde. Promoter analysis of the human genes identifies common elements involved in their regulation which include osmotic response elements, anti-oxidant response elements, xenobiotic response elements, AP-1 sites and steroid response elements. The human AKRs are highly polymorphic, and in some instances single nucleotide polymorphisms (SNPs) of high penetrance exist. This suggests that there will be inter-individual variation in endogenous and xenobiotic metabolism which in turn affect susceptibility to nuclear receptor signaling and chemical carcinogenesis. (c) 2007 Elsevier Inc. All rights reserved.
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