Disease relevance of Aldh1a1

• In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method [1].
• The results suggest that changes in the specific activity and property of ALDH may be a useful tool as a biochemical concomitant to both development and progression of the hepatoma studied [2].
• The E1 protein, acting as a helicase, moved in the 3'-->5' direction, like simian virus 40 (SV40) large tumor antigen, which plays a pivotal role in SV40 DNA replication [3].
• We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase (ALDH) activity to modify disease progression of nmd mice, an animal model of SMARD1 [4].
• A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core and E1 genes of hepatitis C virus (HCV) was constructed [5].

Psychiatry related information on Aldh1a1

• CONCLUSIONS: These data suggest that brain ALDH may contribute to the effects of ethanol on locomotor activity [6].
• Although liver and brain ALDH activities were both significantly higher in D2 than B6, these activities were not related to alcohol consumption [7].

High impact information on Aldh1a1

• Second-site suppressor mutations were uncovered in both E1 and E2 genes that allow for transformation, maintenance, and chromosomal attachment [8].
• Bovine papilloma virus (BPV)-encoded E1 protein contains multiple activities required for BPV DNA replication [3].
• These studies suggested that in particular the expression of ALDH delineated distinct CD34+ stem cell and progenitor compartments [9].
• Cell fractionation according to lineage depletion and ALDH activity provides a viable and prospective purification of HSCs on the basis of cell function rather than cell surface phenotype [10].
• We have purified primitive HSCs from human umbilical cord blood (UCB) by lineage depletion (Lin(-)) followed by selection of cells with high aldehyde dehydrogenase (ALDH) activity [10].

Chemical compound and disease context of Aldh1a1

• Moreover, the treatment with (diethylamino)benzaldehyde, an ALDH inhibitor, completely abolished the toxicity of BA [11].
• Signal recognition particle-dependent insertion of coronavirus E1, an intracellular membrane glycoprotein [12].
• Because the dose-limiting toxicity of cyclophosphamide is myelosuppression, retrovirus-mediated transfer of ALDH-1 to bone marrow cells has been proposed as a protective strategy [13].

Biological context of Aldh1a1

• The phenotypes are inherited in a normal Mendelian fashion, with two alleles showing co-dominant expression at a single locus (Ahd-2) [14].
• Genetics of aldehyde dehydrogenase isozymes in the mouse: evidence for multiple loci and localization of Ahd-2 on chromosome 19 [14].
• Biochemical studies indicate that alcohol dehydrogenase (ADH) metabolizes retinol to retinal, and that aldehyde dehydrogenase (ALDH) metabolizes retinal to retinoic acid, a molecule essential for growth and development [15].
• Biochemical, genetic and molecular genetic analyses have been performed on several of these enzymes, including studies on variant forms of ADH and ALDH [16].
• During the cloning process, an additional closely related gene was also isolated and named Aldh-pb, owing to its high amino acid sequence identity (92%) with the rat phenobarbitol-inducible ALDH protein (ALDH-PB) [17].

Anatomical context of Aldh1a1

• Thus, ADH-IV and ALDH-1, two metabolic enzymes able to convert retinol to retinoic acid, are both initially expressed in primitive streak mesoderm at E7.5 when retinoic acid is first detectable [18].
• Raldh-3 was preferentially expressed first in the surface ectoderm overlying the ventral portion of the prospective eye region and then in the ventral retina, earlier than Raldh-1 in chick and mouse embryos [19].
• Mouse ALDH exhibits extensive multiplicity, several forms of which have been characterized, including ALDH1 (liver cytoplasmic/class 1 isozyme); ALDH2 (liver mitochondrial/class 2.); ALDH3 (stomach cytosolic/class 3); ALDH4 (liver microsomal/class 3); and ALDH5 (testis cytosolic/class 3) [16].
• Injection of ALDH1, but not ALDH-PB, mRNA stimulated retinoic acid synthesis in Xenopus embryos at the blastula stage [17].
• These results could suggest a model for a molecular pathway from androgen receptor to retinoic acid biogenesis in Leydig cells via the mediation of ALDH [20].

Associations of Aldh1a1 with chemical compounds

• Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid [21].
• We now present genetic evidence that aldehyde dehydrogenase Aldh1a1, also known as retinaldehyde dehydrogenase Raldh1, plays a dominant role in the second step of retinol clearance in adult mice [21].
• We also isolated RALDH-1 which is expressed in the chick dorsal retina and implicated in RA formation [19].
• Adh and Aldh gene activity in mouse and rat embryos indicate the possible involvement of the respective enzymes in retinoid metabolism and participation in defense against toxic insults, including those that may be involved in the pathogenesis of PD [22].
• High expression of Aldh 1 mRNA was found in the developing mesencephalic dopamine neurons of both mice and rats [22].

Enzymatic interactions of Aldh1a1

• We previously reported the purification and partial amino acid (aa) sequence of a rat kidney aldehyde dehydrogenase (ALDH) isozyme that catalyzed the oxidation of 9-cis and all-trans retinal to corresponding RA with high efficiency [Labrecque et al. Biochem. J. 305 (1995) 681-684] [23].

Other interactions of Aldh1a1

• Aldh1 spans about 45 kb in length, whereas Aldh-pb spans about 35 kb [17].
• Sphere cells subcultured on plastic exhibited a dendritic morphology characteristic of keratocytes, and maintained keratocan, Aldh, and CD34 expression in serum-free medium [24].
• One vector contained the additional promoter and the MA/CA genes immediately downstream of the VEE E1 gene at the 3' end of the genome [25].

Analytical, diagnostic and therapeutic context of Aldh1a1

• Sequence analysis of eta-crystallin from two genera of elephant shrews and expression of recombinant eta-crystallin show that the protein is a cytoplasmic (class 1) aldehyde dehydrogenase (ALDH1, EC 1.2.1.3) with activity for the oxidation of retinaldehyde to retinoic acid [26].
• Northern blot and RT-PCR-mediated analysis demonstrated that rat kidney ALDH is strongly expressed in kidney, lung, testis, intestine, stomach and trachea, but weakly in the liver [23].
• Alcohol dehydrogenase and aldehyde dehydrogenase (ADH and ALDH) have been coencapsulated into mouse erythrocytes by an electroporation technique [27].
• The expression and localisation patterns of ADH (1-3) and ALDH (1-3) were investigated in the skin and liver of the mouse (BALB/c and CBA/ca), rat (F344) and guinea-pig (Dunkin-Hartley), using Western blot analysis and immunohistochemistry with class-specific antisera [28].
• We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content [29].

References