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Gene Review

Aldh2  -  aldehyde dehydrogenase 2 family...

Rattus norvegicus

Synonyms: ALDH class 2, ALDH-E2, ALDH1, Aldehyde dehydrogenase, mitochondrial
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Disease relevance of Aldh2

  • The p-ALDH expressed in E. coli was a soluble tetrameric protein [1].
  • In the present studies, we aimed to mimic the high-acetaldehyde low-ALDH2 activity phenotype in a rat hepatoma cell line by inhibiting Aldh2 gene expression by an Aldh2 antisense-coding gene carried by an adenoviral vector [2].
  • METHODS: We designed and produced elevated titers of adenoviral vectors (10 virions/ml) carrying Aldh2 cDNA cloned in the reverse orientation preceded by a CMV promoter and followed by a poly-A termination signal [2].
  • Neoplastic nodules and carcinomas possess a wide variety of ALDH staining patterns between and within lesions [3].
  • By histochemistry, total activity assays and gel electrophoresis, only 7 of the 28 (25%) of the hepatic neoplasms examined expressed the tumor-associated ALDH phenotype [4].

Psychiatry related information on Aldh2


High impact information on Aldh2

  • Poly(A)-containing RNA from HTC rat hepatoma cells, which have been shown to possess high levels of tumor ALDH, was used as template to synthesize double-stranded cDNA [7].
  • The cDNA sequence has been confirmed by comparison to the amino acid sequence of tumor ALDH purified from HTC cells [7].
  • Significant changes in aldehyde dehydrogenase (ALDH) activity occur during rat hepatocarcinogenesis in vivo [8].
  • To compare the structure and expression of the tumor aldehyde dehydrogenase gene in rat hepatoma cell lines and normal rat liver, several rat hepatoma cell lines, including HTC, H4-II-EC3, JM2, McA-RH7777, and four lines established in this laboratory have been examined for T-ALDH gene expression using a tumor ALDH complementary DNA [8].
  • An additional five neoplasms had barely detectable levels of benzaldehyde and NADP+ ALDH activity [4].

Chemical compound and disease context of Aldh2


Biological context of Aldh2

  • Overall, the data show that alleles of Aldh2 strongly segregate with the phenotype of ethanol consumption and the relative K(m) for NAD+ of ALDH2 [5].
  • CONCLUSIONS: Data presented show that antialcohol drugs that inhibit Aldh2 gene expression can be generated endogenously in liver cells infected by an adenoviral vector carrying an antisense-coding gene, thus mimicking the high-acetaldehyde phenotype that exists in humans carrying the Glu487Lys mutation who are protected against alcoholism [2].
  • Nevertheless, these amino acids could be exchanged in either RALDH or PB-ALDH without affecting substrate specificity [14].
  • By immunoscreening of a mouse liver cDNA library, we cloned the cDNA coding for DNR-BP54 and we found that this protein is aldehyde dehydrogenase-2 (EC [15].
  • To refine the common amino acid motif for the recognition by Tom20, we introduced a new peptide library approach in this study: we prepared a mixture of ALDH presequence variants, tethered these peptides to DeltaTom20 in a competitive manner by an intermolecular disulfide bond, and determined the relative affinities by MALDI-TOF mass spectrometry [16].

Anatomical context of Aldh2

  • The assembly states of both p-ALDH and m-ALDH synthesized in a rabbit reticulocyte lysate were also determined [1].
  • Thus, we obtained ALDH2-deficient cell lines by introducing mouse mutant Aldh2 cDNA into PC12 cells [17].
  • Areas of cholangiofibrosis, cystic degeneration, and bile duct proliferation were distinctly ALDH negative [4].
  • Significantly, unlike native ALDH precursor protein, the linker-deleted signal peptide precursor protein could no longer be processed after import into mitochondria [18].
  • However, Class 3 ALDH is constitutively expressed at it's highest specific activity in corneal epithelium [19].

Associations of Aldh2 with chemical compounds

  • Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene [20].
  • Benzo(a)pyrene, 3-methylcholanthrene, and phenobarbital induce hepatic ALDH activity after treatment in vivo [21].
  • Treatment with benzo(a)pyrene (1.0 mM) also increases the NADP-dependent ALDH activity in both lines up to 17- and 48-fold, respectively [21].
  • In animals receiving ethionine plus choline deficiency, significant changes in ALDH were observed histochemically by 9 weeks, when there was a distinct shift in activity from its normal centrilobular pattern to a periportal distribution [4].
  • The induction of ALDH is blocked by actinomycin D, alpha-amanitin, and cycloheximide [21].

Other interactions of Aldh2


Analytical, diagnostic and therapeutic context of Aldh2

  • Further studies with this animal model of AML, in which resistance to CY is mediated by elevated ALDH activity, may elucidate mechanisms for effective elimination of drug-resistant leukemic cells ex vivo and in vivo [24].
  • Treatment of cell cultures for 72 hr with 3-methylcholanthrene (1.0 mM) increases the NADP-dependent ALDH activity in H4-II-EC3 and McA-RH7777 cell lines up to 34- and 11-fold, respectively [21].
  • Frozen sections of fresh tissue were stained for ALDH using either propionaldehyde-NAD to detect normal liver ALDH or benzaldehyde-NADP to detect tumor ALDH [3].
  • By week 25, the bladder class 3 ALDH activity of BBN-treated animals was 2 times greater than the control group class 3 ALDH activity [25].
  • Diethylnitrosamine following partial hepatectomy followed by phenobarbital promotion was used to study changes in aldehyde dehydrogenase (ALDH) activity during rat hepatocarcinogenesis [26].


  1. Purification and characterization of catalytically active precursor of rat liver mitochondrial aldehyde dehydrogenase expressed in Escherichia coli. Jeng, J.J., Weiner, H. Arch. Biochem. Biophys. (1991) [Pubmed]
  2. Aldehyde dehydrogenase (ALDH2) activity in hepatoma cells is reduced by an adenoviral vector coding for an ALDH2 antisense mRNA. Karahanian, E., Ocaranza, P., Israel, Y. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  3. Histochemical localization of aldehyde dehydrogenase during rat hepatocarcinogenesis. Lindahl, R., Clark, R., Evces, S. Cancer Res. (1983) [Pubmed]
  4. Changes in aldehyde dehydrogenase occurring during rat hepatocarcinogenesis induced by ethionine combined with dietary choline deficiency. Evces, S., Lindahl, R. Cancer Res. (1986) [Pubmed]
  5. Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor affinity and segregate with voluntary alcohol consumption in rats. Sapag, A., Tampier, L., Valle-Prieto, A., Quintanilla, M.E., Moncada, C., Israel, Y. Pharmacogenetics (2003) [Pubmed]
  6. Alterations in brain aldehyde dehydrogenase activity modify the locomotor effects produced by ethanol in rats. Spivak, K., Aragon, C.M., Amit, Z. Alcohol and drug research. (1987) [Pubmed]
  7. Cloning and complete nucleotide sequence of a full-length cDNA encoding a catalytically functional tumor-associated aldehyde dehydrogenase. Jones, D.E., Brennan, M.D., Hempel, J., Lindahl, R. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  8. Expression of tumor-associated aldehyde dehydrogenase gene in rat hepatoma cell lines. Lin, K.H., Brennan, M.D., Lindahl, R. Cancer Res. (1988) [Pubmed]
  9. Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells. Canuto, R.A., Ferro, M., Salvo, R.A., Bassi, A.M., Trombetta, A., Maggiora, M., Martinasso, G., Lindahl, R., Muzio, G. Biochem. J. (2001) [Pubmed]
  10. Semi-chronic increase in striatal level of 3,4-dihydroxyphenylacetaldehyde does not result in alteration of nigrostriatal dopaminergic neurones. Legros, H., Janin, F., Dourmap, N., Bonnet, J.J., Costentin, J. J. Neurosci. Res. (2004) [Pubmed]
  11. Role of the highly conserved histidine residues in rat liver mitochondrial aldehyde dehydrogenase as studied by site-directed mutagenesis. Zheng, C.F., Weiner, H. Arch. Biochem. Biophys. (1993) [Pubmed]
  12. 3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. Lamensdorf, I., Eisenhofer, G., Harvey-White, J., Nechustan, A., Kirk, K., Kopin, I.J. Brain Res. (2000) [Pubmed]
  13. Ethanol co-exposure increases lethality of allyl alcohol in male Sprague-Dawley rats. Lee, J.Y., Chung, S.M., Lee, M.Y., Chung, J.H. J. Toxicol. Environ. Health Part A (1999) [Pubmed]
  14. Recombinant class I aldehyde dehydrogenases specific for all-trans- or 9-cis-retinal. Montplaisir, V., Lan, N.C., Guimond, J., Savineau, C., Bhat, P.V., Mader, S. J. Biol. Chem. (2002) [Pubmed]
  15. The daunorubicin-binding protein of Mr 54,000 is an aldehyde dehydrogenase and is down-regulated in mouse liver tumors and in tumor cell lines. Banfi, P., Lanzi, C., Falvella, F.S., Gariboldi, M., Gambetta, R.A., Dragani, T.A. Mol. Pharmacol. (1994) [Pubmed]
  16. Peptide library approach with a disulfide tether to refine the Tom20 recognition motif in mitochondrial presequences. Obita, T., Muto, T., Endo, T., Kohda, D. J. Mol. Biol. (2003) [Pubmed]
  17. Deficiency in a mitochondrial aldehyde dehydrogenase increases vulnerability to oxidative stress in PC12 cells. Ohsawa, I., Nishimaki, K., Yasuda, C., Kamino, K., Ohta, S. J. Neurochem. (2003) [Pubmed]
  18. Import, processing, and two-dimensional NMR structure of a linker-deleted signal peptide of rat liver mitochondrial aldehyde dehydrogenase. Thornton, K., Wang, Y., Weiner, H., Gorenstein, D.G. J. Biol. Chem. (1993) [Pubmed]
  19. Constitutive expression of class 3 aldehyde dehydrogenase in cultured rat corneal epithelium. Boesch, J.S., Lee, C., Lindahl, R.G. J. Biol. Chem. (1996) [Pubmed]
  20. Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats. Quintanilla, M.E., Tampier, L. Addiction biology. (2003) [Pubmed]
  21. Regulation of aldehyde dehydrogenase activity in five rat hepatoma cell lines. Lin, K.H., Winters, A.L., Lindahl, R. Cancer Res. (1984) [Pubmed]
  22. Follicle-stimulating hormone and leukemia inhibitory factor regulate Sertoli cell retinol metabolism. Guo, X., Morris, P., Gudas, L. Endocrinology (2001) [Pubmed]
  23. Dopaminergic differentiation of the Nurr1-expressing immortalized mesencephalic cell line CSM14.1 in vitro. Haas, S.J., Wree, A. J. Anat. (2002) [Pubmed]
  24. Development and characterization of a cyclophosphamide-resistant subline of acute myeloid leukemia in the Lewis x Brown Norway hybrid rat. Koelling, T.M., Yeager, A.M., Hilton, J., Haynie, D.T., Wiley, J.M. Blood (1990) [Pubmed]
  25. Changes in aldehyde dehydrogenase during rat urinary bladder carcinogenesis. Campbell, P., Irving, C.C., Lindahl, R. Carcinogenesis (1989) [Pubmed]
  26. Changes in aldehyde dehydrogenase activity during diethylnitrosamine-initiated rat hepatocarcinogenesis. Lindahl, R., Evces, S. Carcinogenesis (1987) [Pubmed]
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