Disease relevance of ALDH1A1

• The present study was undertaken to ascertain the role of ALDH1A1 and -3A1 in HNE metabolism and HNE-induced toxicity in cultured human lens epithelial cells (HLECs) and in rat and mouse lenses [1].
• METHODS: Cellular levels of ALDH1A1 and ALDH3A1 in 171 repository human breast tumor (122 primary and 49 metastatic) samples were semiquantified using immunocytochemical staining [2].
• Molecular cloning and baculovirus expression of the rabbit corneal aldehyde dehydrogenase (ALDH1A1) cDNA [3].
• Partial cDNA clones encoding human cytosolic aldehyde dehydrogenase (ALDH1) and mitochondrial aldehyde dehydrogenase (ALDH2) were isolated from a human liver cDNA library constructed in phage lambda gt11 [4].
• A marked reduction of ALDH1 expression was seen in surviving neurons of SN pars compacta but not of those in the VTA in Parkinson's disease [5].

Psychiatry related information on ALDH1A1

• The alcoholics had significantly lower frequencies of the ADH2*2, ADH3*1, and ALDH2*2 alleles than did the nonalcoholics, suggesting that genetic variation in both ADH and ALDH, by modulating the rate of metabolism of ethanol and acetaldehyde, influences drinking behavior and the risk of developing alcoholism [6].
• The effects of sex, aging, smoking, drinking alcohol, liver function, and various drugs on ALDH activity were also analyzed [7].
• To understand the relationship among alcoholism, antisocial personality disorder, and the protective effects of ADH and ALDH, it is necessary to recruit individuals with antisocial personality disorder but without alcoholism [8].
• These findings clearly distinguish the action(s) of daidzin and daidzein from those of the classic, broad acting inhibitors of ALDH (e.g. disulfiram) and class I ADH isozymes (e.g. 4-methylpyrazole), and identify them as a new class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse [9].
• Erythrocyte ALDH activity can be readily monitored to determine patient compliance and is an accessible model for investigations of in vivo mechanisms of drug inhibition [10].

High impact information on ALDH1A1

• The severe visual impairment of individuals with mutations in RDH12 is in marked contrast to the mild visual deficiency in individuals with fundus albipunctatus caused by mutations in RDH5, encoding another retinal dehydrogenase [11].
• BACKGROUND & AIMS: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans [12].
• Differential expression patterns of ADH and ALDH in the alimentary tract suggest that different vulnerabilities to ethanol-induced mucosal injury may exist [12].
• The gastric ADH and ALDH activities were not significantly different between men and women with respect to age and genetic polymorphism [12].
• Despite the well-established link between the ALDH2*2 allele and the physiological discomforts after drinking, very little is known regarding the psychological expectancies of drinking among persons with alcoholism with different ALDH genotypes [13].

Chemical compound and disease context of ALDH1A1

• Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemotherapeutic regimens [2].
• ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia [5].
• The isoenzyme patterns of ADH and ALDH remained unaltered in colon carcinomas, except that a significant reduction of the enzyme activities was found in the cancer tissue as compared with the adjacent normal portions. it is concluded that human colon mucosa exhibits significant amounts of ethanol- and acetaldehyde-oxidizing activities [14].
• In the present study of a human breast cancer cell line (MCF-7) exhibiting about 6-fold resistance to 4HC (MCF/HC), cellular levels of glutathione (GSH) were increased 1.4-fold, while cytosolic GST and ALDH activities were increased 2.7- and 7.2-fold, respectively, relative to the MCF-7 parental line [15].
• Ra1DH2, expressed in the Escherichia coli BL21(DE3) strain, was purified and crystallized using ammonium sulfate as a precipitant [16].

Biological context of ALDH1A1

• Similarly, inhibition of ALDH1A1 in HLECs by ALDH1A1-specific antisense RNA or SiRNA was associated with decreased oxidation of 3H-HNE and increased susceptibility of the cells to oxidative damage, including apoptosis [1].
• A blood sample was obtained from each participant, and leukocyte DNA was extracted and used to genotype for the presence of the ALDH1A1 promoter polymorphisms [17].
• CONCLUSIONS: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression [18].
• RESULTS: Two polymorphisms, a 17 base pair (bp) deletion (-416/-432) and a 3 bp insertion (-524), were discovered in the ALDH1A1 promoter region: ALDH1A1*2 and ALDH1A1*3, respectively [18].
• These data suggest that ALDH1A1 may contribute to corneal cellular defense against oxidative damage by metabolizing toxic aldehydes produced during UV-induced lipid peroxidation [3].

Anatomical context of ALDH1A1

• RESULTS: Primary breast tumor ALDH1A1 and ALDH3A1 levels were highly predictive of their respective levels in paired metastatic breast tumors present in axillary lymph nodes (r2 = 0.80 and 0.85, respectively) [19].
• We have developed transgenic cell lines to examine the potential for either human ALDH1A1 or ALDH3A1 to protect against damage mediated by these toxic aldehydes [20].
• Most mammalian species express high concentrations of ALDH3A1 in corneal epithelium with the exception of the rabbit, which expresses high amounts of ALDH1A1 rather than ALDH3A1 [3].
• A key finding was the detection of a metabolite, most likely carboxyphosphamide, that is formed only by cytosols from cells expressing either class 3 or class 1 ALDH [21].
• ALDH enzyme activity was also quantitated and immunolabeling was performed to determine the expression of ALDH3A1 in human corneal tissue sections from normal and diseased corneas [22].

Associations of ALDH1A1 with chemical compounds

• As judged by findings in preclinical models, determinants of cellular sensitivity to cyclophosphamide and other oxazaphosphorines include two cytosolic aldehyde dehydrogenases, viz., ALDH1A1 and ALDH3A1 [23].
• BACKGROUND: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid [18].
• Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular content of two aldehyde dehydrogenases, viz ALDH1A1 and ALDH3A1, and glutathione [19].
• A small degree of protection against malondialdehyde was afforded by ALDH1A1, but not ALDH3A1 [20].
• Neither ALDH1A1 nor ALDH3A1 conferred any protection against acrolein, acetaldehyde, or chloroacetaldehyde [20].

Physical interactions of ALDH1A1

• In our previous study on grass carp (Ctenopharyngodon idellus) liver ALDH, a significant amount of the ALDH activity did not adsorb on the alpha-cyanocinnamate Sepharose column which binds ALDH2 [24].

Regulatory relationships of ALDH1A1

• The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development [25].

Other interactions of ALDH1A1

• Resistance was correlated with hALDH-3 activity, and was reversed by pretreatment with the ALDH inhibitor diethylaminobenzaldehyde [21].
• As previously reported in ALDH1 and ALDH2, a higher catalytic efficiency (Vmax/Km) for oxidation of long-chain aliphatic aldehydes was found in ALDH3, suggesting that these enzymes have a hydrophobic barrel-shape substrate binding pocket [26].
• RT-PCR, western blotting and immunolabeling were used to detect mRNA and protein expression of ALDH isozymes and TKT [22].
• The neighbor-joining tree derived from 12 human ALDHs and antiquitin indicates that diversification within the ALDH1/2/5/6 gene cluster occurred during the Neoproterozoic period (about 800 million years ago) [27].
• OBJECTIVE: To ascertain why alcohol is prone to manifest unpleasant effects in diabetes associated with mitochondrial tRNA(Leu(UUR) mutation at position 3243 (DM-Mt3243), we investigated the genotype of aldehyde dehydrogenase (ALDH) 2 and alcohol dehydrogenase 2 (ADH2) in DM-Mt3243 [28].

Analytical, diagnostic and therapeutic context of ALDH1A1

• The therapeutic outcome of cyclophosphamide-based chemotherapy corresponded to cellular ALDH1A1 levels in 77% of cases [2].
• ALDH was detected by activity staining following separation of crude extracts by isoelectric focusing [29].
• Scallop eye lens Omega-crystallin is an inactive aldehyde dehydrogenase (ALDH1A9) related to cytoplasmic ALDH1A1 and mitochondrial ALDH2 that migrates by gel filtration chromatography as a homodimer [30].
• Genomic DNA, isolated from a panel of mouse-human and Chinese hamster-human hybrid cell lines, was digested by restriction endonucleases and subjected to Southern blot hybridization using cDNA probes for ALDH1 and for ALDH2 [31].
• We investigated mRNA expression of the cytosolic aldehyde dehydrogenase (ALDH1), presumably involved in DA degradation, by in situ hybridization in DA neurons of human postmortem material [5].

References