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

• We investigated whether there are differences in the coding regions of ALDH2 cDNA in these lines and whether the Aldh2 genotype predicts the phenotype of alcohol consumption and the K(m) of ALDH2 for NAD+ [5].
• The role of brain aldehyde dehydrogenase (ALDH) and acetaldehyde in mediating ethanol-induced locomotor activity was investigated using several enzyme inhibitors [6].

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

• In conclusion, arachidonic acid added to the culture medium of hepatoma cell lines is able to partially restore the normal phenotype of class 2 ALDH, in addition to a decrease in cell growth [9].
• This work was carried out to evaluate the potential in vivo toxicity of 3,4-dihydroxyphenylacetaldehyde (DOPAL), an aldehyde formed from dopamine by monoamine oxidase (MAO) that is oxidised mainly to 3,4-dihydroxyphenylacetic acid (DOPAC) by brain aldehyde dehydrogenases (ALDH) [10].
• One histidine residue (H235) is conserved in all known aldehyde dehydrogenases (ALDH), from Escherichia coli to human, except for those from P. oleovorans and rat hepatoma [11].
• Both the potentiation of toxicity and the increase in DOPAL levels were blocked by inhibition of monoamine oxidase with clorgyline indicating that accumulation of DOPAL was responsible for the potentiated rotenone-induced toxicity following combined inhibition of ALDH and ARs [12].
• Since allyl alcohol and ethanol are both metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), ethanol could affect allyl-alcohol induced toxicity under in vivo coexposure conditions [13].

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 1.2.1.3) [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

• Levels of AHD-2 (aldehyde dehydrogenase-2) and RALDH-2 (retinaldehyde dehydrogenase-2) messenger RNAs, which encode enzymes that convert [(3)H]retinaldehyde to [(3)H]RA, are increased by about 2-fold by FSH, whereas no change in CYP26 (RA hydroxylase) expression is seen [22].
• This was followed by a time-dependent up-regulation of the enzymes tyrosine hydroxylase and aldehyde dehydrogenase 2 characteristic of mature dopaminergic neurones [23].

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].

References