Mouse dioxin-inducible cytosolic aldehyde dehydrogenase-3: AHD4 cDNA sequence, genetic mapping, and differences in mRNA levels
| Autor: | Vasiliou, Kozak Ca, Daniel W. Nebert, Steven F. Reuter |
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| Předmět: |
Male
DNA Complementary Polychlorinated Dibenzodioxins Molecular Sequence Data Aldehyde dehydrogenase Dioxins chemistry.chemical_compound Mice Cytosol Gene mapping Complementary DNA Genetics Tumor Cells Cultured Animals Amino Acid Sequence RNA Messenger General Pharmacology Toxicology and Pharmaceutics Gene Derepression Southern blot Methionine biology Base Sequence Chromosome Mapping Aldehyde Dehydrogenase Molecular biology Mice Inbred C57BL chemistry Liver Cell culture Mice Inbred DBA Enzyme Induction biology.protein Female |
| Zdroj: | Europe PubMed Central |
| Popis: | We have cloned and sequenced the murine AHD4 cDNA encoding the 'Class 3' cytosolic aldehyde dehydrogenase (ALDH-3c). The cDNA is 1722 bp in length, excluding the poly(A+) tail, and has 5' and 3' nontranslated regions of 174 bp and 186 bp, respectively. AHD4 encodes a protein of 453 amino acids, including the first methionine (M(r) = 50,466). The murine AHD4 protein is 91% and 80% similar to the rat and human ALDH3c proteins, respectively, 64% identical to the rat microsomal ALDH3 protein, and < 28% similar to ALDH 'Class 1' and 'Class 2' proteins. Surprisingly, in contrast to the rat gene that is expressed in both cell cultures and the intact liver, the murine Ahd-4 gene is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) or benzo[a]pyrene in cell cultures but not in liver of the intact adult or newborn mouse. Southern hybridization analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4 gene is likely to span less than a total of 15 kb, and was mapped to chromosome (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses. AHD4 mRNA levels are strikingly elevated in the untreated mouse hepatoma Hepa-1c1c7 mutant line c37 lacking CYP1A1 (aryl hydrocarbon hydroxylase) activity and in the untreated 14CoS/14CoS mouse cell line having a homozygous deletion of about 1.2 cM on Chr 7. Our data suggest that the Ahd-4 gene in murine cell cultures is regulated by three distinct mechanisms: Ah receptor-mediated induction by TCDD or benzo[a]pyrene, CYP1A1 metabolism-dependent repression, and Chr 7-mediated putative derepression. |
| Databáze: | OpenAIRE |
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