Disease relevance of Aldh1a1

• Cloning of a rat cDNA encoding retinal dehydrogenase isozyme type I and its expression in E. coli [1].
• Vitamin A deficiency induced squamous metaplasia in the tracheal epithelium and down-regulated RALDH expression [2].

High impact information on Aldh1a1

• Cotransfection, mutagenesis, and gel retardation experiments implicated the hypoxia-inducible factor 3alpha/aryl hydrocarbon nuclear translocator heterodimer for Aldh1a1 promoter activation via the XREs and stimulated by retinoic acid protein 13 for promoter repression via the E-box [3].
• Characterization of chimeric enzymes demonstrates that distinct groups of amino acids control the differential activity of RALDH and PB-ALDH with all-trans- and 9-cis-retinal [4].
• On the other hand, recombinant RALDH efficiently catalyzed oxidation of 9-cis- and all-trans-retinal, whereas PB-ALDH was inactive with all-trans-retinal and poorly active with 9-cis-retinal [4].
• Nevertheless, these amino acids could be exchanged in either RALDH or PB-ALDH without affecting substrate specificity [4].
• First, retinol is converted into retinal by a retinol dehydrogenase, and, subsequently, retinoic acid is formed by a retinal dehydrogenase [5].

Biological context of Aldh1a1

• A retinol dehydrogenase that we have previously described, eRolDH, and the retinal dehydrogenase, RalDH II, were found to have markedly increased uterine mRNA levels within 4 h of E2 administration, independent of the prior administration of puromycin. eRolDH and RalDH II and their mRNAs were also increased in uteri of rats during estrus [6].
• Retinal dehydrogenase gene expression in stomach and small intestine of rats during postnatal development and in vitamin A deficiency [7].
• Here we show immunohistochemical localization of the retinol binding protein receptor, cellular retinol binding protein, retinol dehydrogenase and retinal dehydrogenase in rat embryos (presomitic to the 25-30 somite pair stage) [8].
• We have recently shown the expression of RALDH transcript in the stomach and small intestine by reverse transcription polymerase chain reaction [Bhat, P.V., Labrecque J., Dumas, F., Lacroix, A. and Yoshida, A. (1995) Gene 166, 303-306] [7].
• RALDH catalyzes the oxidation of retinal to retinoic acid, which regulates cell growth and differentiation by activating retinoic acid receptors [9].

Anatomical context of Aldh1a1

• The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons [10].
• Cellular expression of retinal dehydrogenase types 1 and 2: effects of vitamin A status on testis mRNA [11].
• A basic pI retinal dehydrogenase has been purified recently that accounts for approximately 90% of the all-trans-retinal dehydrogenase activity of rat liver cytosol [12].
• We have examined RALDH expression in the stomach and small intestine before and during postnatal development and in vitamin A deficiency by assaying for mRNA levels and protein as well as for enzyme activity [7].
• RALDH2 was the only detectable RALDH present in the control or injured spinal cord [13].

Associations of Aldh1a1 with chemical compounds

• We examined the extrarenal and glomerular expression of the retinol (RoDH) and retinal (RalDH) dehydrogenases 1 and 2 as well as the expression of the retinoic acid (RAR) and retinoid X (RXR) receptor subtypes alpha, beta, and gamma [14].
• We have previously characterized and cloned from kidney tissues the rat retinal dehydrogenase type 1 (RALDH1), which oxidizes all-trans and 9-cis retinal with high efficiency but is inactive with 13-cis retinal [15].
• After phenobarbital administration, hepatic retinal dehydrogenase activity was increased 8-fold, but no extrahepatic induction was observed [16].
• Increased hepatic retinal dehydrogenase activity after phenobarbital and ethanol administration [16].
• Retinal dehydrogenase (RALDH) catalyzes the oxidation of retinal to all-trans and 9-cis retinoic acid, which function as ligands controlling RAR and RXR nuclear receptor-signaling pathways [7].

Other interactions of Aldh1a1

• This retinal dehydrogenase was not feedback-inhibited by all-trans- or 9-cis-retinoic acid, nor by holocellular retinoic acid-binding protein, but was stimulated modestly by apocellular retinoic acid-binding protein, an effect not observed in the presence of cellular retinol-binding protein [12].

Analytical, diagnostic and therapeutic context of Aldh1a1

• We examined expression of retinal dehydrogenase (RALDH) types 1 and 2 in liver and lung, and the effect of vitamin A status on testis expression by in situ hybridization [11].
• We also examined the cell-specific localization of RalDH II by immunohistochemistry [6].
• Cytosolic retinal dehydrogenase (EC 1.2.1.36, retinal: NAD+ oxidoreductase) activity was measured by assessing the conversion of retinal to retinoic acid by HPLC [16].

References