Disease relevance of Aldh3a1

• The dioxin-mediated upregulation of Aldh3a1 expression in mouse hepatoma Hepa-1c1c7 cell cultures was shown to depend exclusively on the aromatic hydrocarbon receptor [1].

High impact information on Aldh3a1

• Mouse cytosolic class 3 aldehyde dehydrogenase (Aldh3a1): gene structure and regulation of constitutive and dioxin-inducible expression [1].
• The mouse cytosolic aldehyde dehydrogenase ALDH3A1 (encoded by the Aldh3a1 gene) has previously been shown in cell culture to be markedly inducible by 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), downregulated by the metabolism of functional CYP1A1/1A2 enzymes, and upregulated by a gene on Chr 7 that leads to endogenous oxidative stress [1].
• The dioxin-mediated upregulation of Aldh3a1 expression in mouse hepatoma Hepa-1c1c7 cell cultures was shown to depend exclusively on the aromatic hydrocarbon receptor. acetyltransferase (CAT) or luciferase (LUC) reporter genes, were studied [1].
• In order to study the regulation of Aldh3a1 gene expression, we isolated two overlapping genomic sequences from a B6/CBA mouse genomic library that included the entire Aldh3a1 gene, along with considerable 5' and 3' flanking sequences [1].
• The Aldh3a1 gene was shown to span approximately 10 kb and comprise 11 exons including a noncoding first exon [1].

Biological context of Aldh3a1

• 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 [2].
• In conclusion, we expect one or more putative electrophile response elements (EpRE), previously found in the regulatory regions of the murine Nmol, Ahd4, and ugt1*06 genes, to be functional in responding to phenolic antioxidants [3].
• The phenotypes were inherited in a normal mendelian fashion, with two alleles at a single locus (Ahd-4) showing codominant expression [4].
• Recombination studies have indicated, however, that Ahd-4 and Ahd-6 are distinct but closely linked loci on the mouse genome [5].
• Genetics of ocular NAD+-dependent alcohol dehydrogenase and aldehyde dehydrogenase in the mouse: evidence for genetic identity with stomach isozymes and localization of Ahd-4 on chromosome 11 near trembler [4].

Regulatory relationships of Aldh3a1

• The results thus suggest that Aldh-3 gene is regulated by a mechanism independent of the Ah receptor [6].

Other interactions of Aldh3a1

• DHII treatment of wt cells for 12 hr markedly elevated the enzyme activities and mRNA levels of genes in the [Ah] battery: aryl hydrocarbon hydroxylase (Cyp1a1), NAD(P)H:menadione oxidoreductase (Nmol), cytosolic aldehyde dehydrogenase class 3 (Ahd4), and UDP-glucuronosyltransferase form 1*06 (Ugt1*06) [3].
• We have studied three Phase II genes in the mouse dioxin-inducible [Ah] battery: Nmo1 [encoding NAD(P)H:menadione oxidoreductase], Ahd4 (encoding the cytosolic aldehyde dehydrogenase ALDH3c), and Ugt1*06 (a UDP glucuronosyltransferase) [7].
• The mouse Ahd3 gene is very tightly linked to the Ahd4 gene on chromosome 11 [8].

References