Background: Aberrations in gene methylation patterns play important roles in gliomagenesis. However, whether the ALDH1A3 promoter methylation is related to prognoses of primary glioblastomas (GBMs) in Western China remains unclear. Materials and Methods: Methylation levels of ALDH1A3 CpG island in 36 GBMs were identified by pyrophosphate sequencing, while ALDH1A3 expression was assessed with matched paraffin section immunohistochemistry. Survival curves were analysed by Kaplan-Meier. Results: The hypermethylation status of ALDH1A3 promoter predicted a better prognosis accompanied with low expression of ALDH1A3 protein. Conclusions: Our results indicate ALDH1A3 promoter methylation correlates with prognosis in primary GBMs.
Aldehyde dehydrogenase (ALDH) plays an important role in alcohol metabolism; ALDH is responsible for the oxidation of acetaldehyde generated during alcohol oxidation. ALDH is also known to oxidize various other endogenous and exogenous aldehydes. Cytochrome P-450 2E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol and can be induced by other inducers including acetone and ethanol. We examined single nucleotide polymorphisms (SNP) of ALDH and CYP2E1 genotypes in Korean. Restriction fragment length polymorphism (RFLP) method was used to determine ALDH and CYP2E1 SNP. Mutation in ALDH was 60% (heterozygote 46.7% and homozygote 13.3%) among 15 cases. CYP2E1 mutation was 52.7% (heterozygote 47.4% and homozygote 5.3%) among 19 cases.
Sprague-Dawley rats were given freely with 15% ethanol (control) and 15% ethanol containing (1) 0.1% ginseng saponin, (2) 0.02% ginsenoside $Rb_1$, and (3) $Rg_1$ (tests) instead of water for 7 days and aldehyde dehydrogenase (ALDH) and monoamine oxidase (MAO) activity in different regions of brain were examined. In control group, total ALDH activity with indoleacetaldehyde and acetaldehyde as substrate in all different regions was lower than that of normal group except in the hippocampus. The inhibitory effect on the activity was prominent in the corpus striatum and was not in the hippocampus. However, low-$K_m$ ALDH activity in all different regions was much lower than that of normal group. A considerable decrease in mitochondria ALDH activity in cerebellum and striatum was also observed in control group. In test groups total, low-$K_m$, and mitochondria AkDH activities in all different regions were higher than those in control group. Although ALDH activity in the striatum of test group was higher than control group, it was relatively depressed as compared with normal. There was not found a remarkable difference in extent of stimulating effect on the AkDH activity according to the ginseng saponin components. When biogenic aldehydes were used as substrate, ALDH activity with 3,4-dihydroxy-phenylacetaldehyde (DOPAL) in all brain regions of control group was lower than that using 5-hydroxy-indoleacetaldehyde (HIAL) and 3,4-dihydroxyphenylglycolaldehyde (NORAL) as substrate. In control group, ALDH activity with biogenic aldehydes above mentioned was markedly inhibited in the striatum contrary to other regions. The higher ALDH activity with biogenic aldehydes in test group than in control was found in the striatum, cerebrum, and cerebellum. MAO activity in the cerebellum was inhibited in control group and slightly increased in test group. The results of present study suggest that the corpus striatum is significantly affected by ethanol exposure while the hippocampus is not and that ginseng saponin fraction and ginsenosid es might have a preventive effect against depression of brain ALDH activity by chronic administration of ethanol.
Objectives:The purpose of this study is to evaluate the pathophysiology of alcoholics by investigating the differences in frequency of Aldehyde Dehydrogenase 2(ALDH2) genotypes and ALDH2 alleles between patients with alcohol dependence and controls, and the differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances. Methods:The authors selected 98 patients with alcohol dependence and 53 controls. Self-report questionnaires for acute reponses after alcohol ingestion, the AUI(Alcohol Use Inventory), and the NEO-PI-R(NEO Personality Inventory Revised) were given to all patients with alcohol dependence. ALDH2 genotypes were typed with MboII RFLP(Restriction Fragment Length Polymorphism) method in 53 controls and 98 patients with alcohol dependence. The authors divided alcoholic patients into two groups according to the presence of variant $ALDH2^2$ allele;normal ALDH2 alcoholics(N=87) and variant ALDH2 alcoholics(N=11). Results:1) The genotypic frequencies of subjects with $ALDH2^{1/1}$ were higher and those with $ALDH2^{1/2}$ and $ALDH2^{2/2}$ were lower in patients than in controls. 2) Alcohol dependence could be found in $ALDH2^{2/2}$ homozygote individuals. 3) Variant ALDH2 alcoholics had more family problems in the AUI than normal ALDH2 alcoholics. 4) Variant ALDH2 alcoholics experienced more flushing and cardiovascular responses after alcohol ingestion than normal ALDH2 alcoholics. 5) Variant ALDH2 alcoholics had less altruistic personality traits in the NEO-PI-R than normal ALDH2 alcoholics. 6) Variant ALDH2 alcoholics tended to have more tolerance to alcohol than normal ALDH2 alcoholics. Conclusion:Variant $ALDH2^2$ allele might play a protective role in the pathogenesis of alcohol dependence and there were several significant differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances.
The changes in aldehyde dehydrogenase(ALDH, E.C. 1.2.1.3.) activity in neurons and astrocytes isolated from rat brains were investigated after administration of ethanol and Korean red ginseng(Panax ginseng C.A. Meyer) saponln. The cerebral ALDH activity with acetaldehyde and Propionaldehyde was higher in the white matter than in the gray matter. However, using indole-3-a-cetaldehyde and 3,4-dihydroxyphenylacetaldehyde as substrates, there was no significant difference in activity between two regions in cerebrum. In ethanol treated group, ALDH activity with all the substrates in the gray and white matter was lower than in normal group. In ethanol-saponin treated group, the enzyme activity in the white matter remarkably Increased. The ALDH activity in neurons isolated from cerebral cortex in ethanol-treated group was lower than in normal group. In ethanol-saponin treated group, neuronal ALDH activity with propionaldehyde was significantly recovered but not with Indole-3-acetaldehyde. In astrocytes, although the ALDH activity with propionaldehyde in the ethanol-treated group was not changed as compared with normal group, considerable increase in activity was found in ethanol-saponin treated group. These results suggest that Korean red ginseng saponin may protect the neuronal functions from the toxic effects of acetaldehyde derived from ethanol by stimulation of ALDH activity in astrocytes surrounding nerve cells.
Han, Sang Mi;Hong, In Pyo;Woo, Soon Ok;Kim, Se Gun;Jang, Hye Ri
Journal of Apiculture
/
v.32
no.3
/
pp.269-273
/
2017
We investigated whether purified bee venom increases the enzymatic activity of the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH and ALDH assay were tested by in vitro kits. The purified bee venom was assayed by ultra performance liquid chromatography, The contents of melittin, apamin and phospholipase A2, as main component of purified bee venom, were 63.9%, 2.3%, and 10.9%, respectively. The ADH and ALDH acitivity of purified bee venom(at 1mg/ml) were $88.6{\pm}7.34%$ and $94.6{\pm}0.57%$, respectively compared with positive control at 2mg/ml. These results showed that purified bee venom induces the activity of ADH and ALDH which reduce the aldehyde concentration in the blood, suggesting the possibility of purified bee venom as resource of medicine or functional beverage for hangover relieving.
An, Yoo-Jin;Cho, Sung-Min;Kim, Min-Su;Moon, Hae-Hee;Park, Dong-Soo;Jeon, Nam-Gen;Lee, oungjae;Han, Chang-Hoon
Korean Journal of Veterinary Research
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v.57
no.3
/
pp.147-154
/
2017
The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of $16{\mu}L/mL$. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol ($40.02{\pm}33.38{\mu}g/mL$, $66.01{\pm}22.04{\mu}g/mL$, respectively) and aldehyde ($5.72{\pm}0.47{\mu}g/mL$, $6.72{\pm}1.70{\mu}g/mL$, respectively) concentrations in blood compared to those in the alcohol-water group ($199.75{\pm}33.83{\mu}g/mL$, $50.43{\pm}13.88{\mu}g/mL$, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.
The activity of aldehyde dehydrogenase (ALDH) in the cerebrum, cerebellum, striatum, and medulla oblongata was examined and mitochondrial matrix ALDH was purified prior to immunohistochemical study on the localization of ALDH isozymes in pig brain. Relatively high enzyme activity was found in the striatum and medulla oblongata when using indole-3-acetaldehyde as substrate, and in the striatum when using 3,4-dihydroxyphenylacetaldehyde (DOPAL). The main part of mitochondrial ALDH activities with both acetaldehyde and DOPAL existed in the matrix fraction. The ratio of activity of the matrix to the membrane fraction in the cerebrum was higher than in the cerebellum, suggesting that the distribution pattern of ALDH isozymes was different according to the brain regions. The 276-fold purified mitochondrial matrix ALDH from pig brain was identified to be homologous tetramers with 53 KD subunits. The enzyme showed maximal activity at pH 9.0 and was stable in the temperature range from $25^{\circ}C$ to $37^{\circ}C$. The mitochondrial matrix ALDH activity was considerably inhibited by acetaldehyde in vitro. The $K_m$ values of the enzyme for acetaldehyde and propionaldehyde were 5.8 mM and 4.9 mM, respectively, whereas $K_m$ values for indole-3-acetaldehyde and DOPAL were 44 ${\mu}M$ and 1.6 ${\mu}M$, respectively. The $V_{max}/K_{m}$ ratio was the highest with DOPAL as compared with other substrates. These results suggested that mitochondrial matrix ALDH in the present work might be a low Km isozyme involved in biogenic aldehyde oxidation in pig brain.
Shin, Chol;Kwack, KyuBum;Cho, Nam H.;Kim, Seong Hwan;Baik, Inkyung
Nutrition Research and Practice
/
v.9
no.1
/
pp.79-86
/
2015
BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.
Kim, Cheong-Sik;Koh, Sang-Baek;Kim, Hyeong-Su;Park, Sue-Kyung;Chang, Soung-Hoon
Journal of Preventive Medicine and Public Health
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v.37
no.4
/
pp.321-328
/
2004
Objectives : The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism. Methods : Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood. Results : 1. The urinary concentrations of o-, m-, and p-methylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p<0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p<0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p>0.05). Conclusions : Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed.
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