• Title/Summary/Keyword: ALDH1A3

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Effects of Alcohol on Neurocognitive Function, Psychomotor Performance and Subjective Response in Koreans with Different ALDH2 Genotypes (한국인에서 Aldehyde Dehydrogenase 2 유전자 변이가 알코올의 신경인지 기능, 정신운동성 수행 및 주관적 반응에 미치는 영향)

  • Shin, Il-Seon;Yoon, Jin-Sang;Kim, Hyun;Yoon, Bo-Hyun;Lee, Hoon;Jung, Jae-Sung;Lee, Hyung-Yung
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.176-188
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    • 1999
  • Objective : The purpose of this study was to evaluate the effects of alcohol on neurocognitive function, psychomotor performance and subjective response in healthy Korean adults with different ALDH2 genotypes. Method : A total of 24 males, half with active $ALDH2^*1/2^*1$ and the other with inactive $ALDH2^*1/2^*2$, was selected through genotyping using restriction fragment length polymorphism. In a double-blind, placebo-controlled cross-over design, each subject consumed 0.5g/kg dose of alcohol, given as a mixture of 40% vodka and orange juice, and placebo(orange juice) on two separate occasions on an average of weekly intervals. The blood alcohol concentrations(BACs) were measured using a breath analyzer at baseline and at 30, 60 minutes after drinking. P300s were measured at baseline and at 30 minutes after alcohol and placebo intake. Vital signs and psychomotor performance[Critical Flicker Fusion Threshold(CFFT), Choice Reaction Time (CRT), Digit Symbol Substitution(DSS)] were measured at baseline and at 60 minutes after alcohol and placebo intake. Subjective responses were measured at the end of the study. The statistical analysis focused on whether there were any differences between groups with different ALDH2 genotypes. Results : The major results are as follows. 1) BACs in the inactive group were overall equivalent to those in the active group. Only in terms of time, BACs were significantly higher overall at 30 minutes than at 60 minutes after alcohol intake. 2) Pulse rates were significantly increased after alcohol intake compared with placebo, and the increase was greater in the inactive than in the active group. 3) P300 latencies in leads Fz(frontal), Cz(cental) and Pz(parietal) were significantly increased after alcohol intake compared to placebo, and the increase was greater in the inactive than in the active group. P300 amplitudes in leads Cz and Pz were significantly decreased overall after alcohol intake compared to placebo. 4) Compared with placebo, alcohol produced significant effect on the psychomotor performance : impairment in the inactive group, improvement in the active group. 5) Compared with placebo, alcohol significantly induced a negative or an intense effect on the subjective responses in the inactive group, but little negative and even a somewhat positive effect in the active group. Conclusions : These results suggest that ALDH isozyme variance might be an important factor to determine the effects of acute dose of alcohol on the various psychobehavioural functions and also to determine the alcohol use pattern and to predict the future development of alcohol overuse and/or abuse.

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Gene Expression Profiles in Genetically Different Mice Infected with $Toxoplasma$ $gondii$: ALDH1A2, BEX2, EGR2, CCL3 and PLAU

  • Ismail, Hassan Ahmed Hassan Ahmed;Quan, Juan-Hua;Wei, Zhou;Choi, In-Wook;Cha, Guang-Ho;Shin, Dae-Whan;Lee, Young-Ha;Song, Chang-June
    • Parasites, Hosts and Diseases
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    • v.50 no.1
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    • pp.7-13
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    • 2012
  • $Toxoplasma$ $gondii$ can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after $T.$ $gondii$ infection is not known much. We selected 5 genes ($ALDH1A2$, $BEX2$, $CCL3$, $EGR2$ and $PLAU$) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with $T.$ $gondii$. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI ($P$<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, $T.$ $gondii$-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did $T.$ $gondii$-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.

Effects of Alcohol Intake, Genotypes of Aldehyde Dehydrogenase 2 and N-Acetyltransferase 2 on the Development of Laryngeal Cancer in Koreans (한국인의 후두암 발생에서 음주, Aldehyde Dehydrogenase 2(ALDH2)와 N-Acetyltransferase 2(NAT2) 유전자 다형성의 역할)

  • Kwon Soon-Uk;Shim Yoon-Sang;Lee Yong-Sik;Hong Seong-Chool;Kim Kwang-Il;Hong Young-Joon;Hong Seok-Il;Kim Hyun-Joo;Kim Heon;Lee Guk-Haeng
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.2
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    • pp.131-138
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    • 2001
  • Objectives: Alcohol intake has been reported to be a risk factor of laryngeal cancer. Since the aldehyde dehydrogenase 2 (ALDH2) genotype is a major determinant of personal alcohol drinking habit, there is a possibility that ALDH2 genotype would be a risk factor for laryngeal cancer. N-Acetyltransferase 2 (NAT2) is a detoxifying enzyme and its polymorphism has been reported to be related to the risk of many environmental cancers. However, studies on the associations between these two genotypes and laryngeal cancer risk are scarce. We have assessed the effects of alcohol intake and the genotype of ALDH2 and NAT2 on the risk of laryngeal cancer in Koreans. Materials and Methods: Eighty-four pathologically proven laryngeal cancer patients and 168 age matched controls were included as the study subjects. Information about alcohol intake and smoking habit was collected using a self administered questionnaire. ALDH2 and NAT2 genotypes were analyzed using PCR-RFLP methods. Results: Alcohol intake was significant as a risk factor for laryngeal cancer (OR : 2.58, 95% CI : 1.24, 5.36), especially for supraglottic laryngeal cancer (OR : 3.24, 95% CI : 1.02, 10.31). Personal drinking habit was closely related with personal smoking habit, which was a potent risk factor of laryngeal cancer. In a stratified analysis according to the level of cumulative smoking amount, drinking was significant neither in light smokers (equal or less than 30 pack-years) nor in heavy smoker (over 30 pack-years). The ALDH2 genotype was significantly associated with the risk of laryngeal cancer in a univariate analysis. The statistical significance, however, disappeared after adjusting alcohol intake using a multiple conditional logistic model. The NAT2 genotype was not significant as a risk factor for laryngeal cancer. Conclusion: Alcohol drinking and ALDH2 genotype would have indirect effects on laryngeal cancer by their correlations with cigarette smoking or with alcohol drinking. It is less likely that the NAT2 genotype would be a potent risk factor of laryngeal cancer.

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Effects of Alcohol on Psychomotor Performance and Subjective Assessments In Normal Adults with Variation of Acetaldehyde Dehydrogenase I (정상성인에서 ALDH-I의 변이가 알콜의 정신운동성 수행과 주관적 평가에 미치는 영향)

  • Yoon, Bo Hyun;Yoon, Jin Sang
    • Korean Journal of Biological Psychiatry
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    • v.3 no.2
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    • pp.222-239
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    • 1996
  • The purpose of this study was to evaluate the effects of alcohol on the psychomotor performance and subjective assessment in healthy Korean adults with acetaldehyde dehydrogenase I(ALDH-I) isozyme variance. A total of 20 male subjects, half with active ALDH-I and the other half with inactive ALDH-I, were selected through both a self-reporting questionnaire examining alcohol sensitivity and the Higuchi's ethanol patch test detecting ALDH-I deficiency. In a doule-blind, placebo-controlled cross-over design, each subject consumed four doses of alcohol(0.25, 0.5, 0.75, 1.0g/kg) and placebo on five separate occasions at weekly intervals, Treatment order was fully balanced using a $5{\times}5$ Latin square, Psychomotor performance tests[coritical flicker fusion threshold(CFF) and choice reaction time(CRT)] and self-estimate questionnaires were conducted at baseline and at time points of 20, 40, 60, 90, 120, 150, 180 minutes after consuming the test drug for 20 minutes, Blood alcohol concentrations(BACs) using breath analyzer were measured at baseline and at time points of 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180 minutes after drinking, The BACs and the mean changes in the psychomotor performances and subjective assessments from pre-alcohol baseline, were compared between the two groups. The findings were summarized as follows : 1) BACs were tended to be higher in the inactive group than the active in all of the four alcohol doses. However significant group differences were only after the 0.5g/kg dose of alcohol. 2) The inactive group showed significant impairment in CFFT at most time points alter 0.75 and 1.0g/kg doses of alcohol. 3) In CRT, total reaction time(TRT) significantly prolonged in the inactive group than the active group at 20 minutes after 0.25 and 1.0g/kg doses of alcohol and at 40, 60, 90 minutes alter 0.75g/kg dose of alcohol. In the inactive group, recognition time component significantly increased at 20, 60, 90 minutes after 1.0g/kg dose of alcohol, while movement time component significantly increased at 40, 60 minutes after 0.75g/kg dose of alcohol. 4) Subjective evaluation of the effect of alcohol revealed that physical and mental conditions as well as a self-estimate of the effects of alcohol on performance were significantly worse in the inactive group than the active at some time points alter all of the lour alcohol doses, wihch were more pronounced after 0.75 and 1.0g/kg doses of alcohol. 5) Most of the group differences mentioned above, still remained statistically significant after BAC was entered as a covariate, These findings demonstrated that the alcohol sensitivity is higher in individuals with inactive ALDH-I than those with active ALDH-I both on the subjective assessments and the objective psychomotor performances. Furthermore, these results suggest thai the alcohol sensitivity may be determined by acetaldehyde concentration rather than BAC per se. In future studies, after more accurate genotyping for ALDH-I, the relationships between BAC, acetaldehyde concentration and alcohol sensitivities should be clearly defined.

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p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

  • Ferronika, Paranita;Triningsih, F.X. Ediati;Ghozali, Ahmad;Moeljono, Abraham;Rahmayanti, Siti;Shadrina, Arifah Nur;Naim, Awang Emir;Wudexi, Ivan;Arnurisa, Alfa Monica;Nanwani, Sandeep Tarman;Harijadi, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1943-1948
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    • 2012
  • Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

Effect of Ginseng Saponin on Alcohol Metabolism in the Animal Body (인삼사포닌이 동물생체의 주정대사에 미치는 영향)

  • Joo, Chung-No
    • Journal of Ginseng Research
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    • v.16 no.3
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    • pp.222-227
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    • 1992
  • Unlike carbohydrats and fats, alcohol is essentially foreign to the body and it is known that the body get rid of it by oxidizing alcohol maily in the liver. Acetaldehyde is produced during ethanol metabolism and is known to be oxidized mainly by aldehyde dehydrogenase (ALDH). ALDH activity was found mainly in the mitochondrial fraction but a significant ALDH activity was also present in microsomal and cytosol fraction. Wistar rats (150~200 g, male) were given freely with 12% ethanol (Control) and/or 12% ethanol containing 0.1% ginseng saponins (Test) instead of water for 6 days and the liver was analyzed. ALDH activities of both control and test group were lower than that of normal group but test AkDH was less inhibited than control. ADH activies of both control and test were slightly higher than that of normal group but our previous data showed that it became gradually steady after prolonged ethanol feeding. MEOS activities of both control and test group were much higher than that of normal group. MEOS enzymes are inducible but the activity of test group was greatly higher than that of control. Ethanol containing [1-i4C] ethanol (5 $\mu$Ci) was injected to the above three groups and 30 min later, the distribution of radioactivity of hepatic lipids was investigated. Radioactivities of hepatic lipids of both control and test group were higher than that of normal group, however, that of test group was much lower than that of control. Analysis of individual lipids showed that phospholipid biosynthesis was significantly impaired and fatty acid and triglycerides biosynthesis were greatly stimulated. However, it was realized that the saponin prevented phospholipid biosynthesis depression and the increase of triglyceride biosynthesis considerably. It seemed that the saponin might stimulate ADH, ALDH and MEOS and the acetaldehyde formed would be removed faster. The excess hydrogen can be shunt more quickly into lipid biosynthesis. Electron microscopic observation showed that the hepatic cell of control group was si gnificantly damaged. Mitochondria were swollen and rough endoplasmic reticulum were dilated, however, hepatocytes of test group were not damaged.

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Effects of Aqueous Medicinal Herb Extracts and Aqueous Fermented Extracts on Alcohol-Metabolizing Enzyme Activities (약용식물의 열수추출물과 적정 조성추출물 및 그 발효물이 알콜대사 효소활성에 미치는 영향)

  • Lee, Ka-Soon;Kim, Gwan-Hou;Seong, Bong-Jae;Kim, Hyun-Ho;Kim, Mi-Yeon;Kim, Mee-Ree
    • Food Science and Preservation
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    • v.16 no.2
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    • pp.259-265
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    • 2009
  • To develop an effective anti-hangover product, hot-water extracts of 25 medicinal herbs were screened for inhibition or activation of alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH), and 12 herbs were selected for further study. Chosen medicinal herb extracts(CMHEs) were fermented by Lactobacillus delbruechii subspecies lactis for 10 days at $35^{\circ}C$ after saccharification with nuruk(malt inoculated by 5 types of microbs) for 72 hours at $35^{\circ}C$ and both CMHEs and fermented CMHEs(FCMHEs) were explored for anti-hangover effects in vitro. We found significant ADH inhibition by hot-water extracts of Pueraria thunbergiana, Hovenia dulcis Thunb, Lycium chinense, Glycyrrhiza uralensis, Acanthopanax sessiliflorus, Liriope platyphylla, and Ixeris dentata, and significant ALDH activation by extracts of Acanthopanax sessiliflorus, Lycium chinense, Ixeris dentata, and Polypori umbellati of the Polyporaceae. The ADH effects on CMHE and FCMHE were -20.22% and -62.63% of control values, and the ALDH effects 173.20% and 280.17%, respectively. In rats given 20%(v/v) alcohol(15 mL/kg), FCMHEs significantly decreased blood acetaldehyde concentrations on 3 hours after ethanol administration, in a dose-dependent manner(p<0.05). Notably, blood acetaldehyde concentrations were markedly reduced in animals given FCMHEs(400 mg/kg) compared to levels seen in rats receiving CADB(commercial alcohol detoxification beverage). Thus, anti-hangover effects were promoted by fermentation of certain medicinal herb extracts.

Changes in Alcohol Dehydrogenase (ADH) and Acetaldehyde Dehydrogenase (ALDH) Activity during the Processing of Salt-Dried Rockfish Sebastes schlegeli (염건 조피볼락(Sebastes schlegeli) 제조 중 ADH 및 ALDH의 활성변화)

  • Shim, Kil Bo;Lee, Hyun Jin;Lee, So Jeong;Cho, Hyun Ah;Yoon, Na Young;Lim, Chi Won
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.45 no.6
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    • pp.594-599
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    • 2012
  • The objective of this study was to determine the processing conditions for salt dried rockfish Sebastes schlegeli by sun drying and cold-air drying, as measured by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. We processed salt dried rockfish samples. The salinity of rockfish samples was within 1% following salting with 25% salt brine for 3 h. The moisture content of salt dried rockfish was found to reduce linearly from 70.12 to 39.5 g/100 g over the same time interval. The water activities of salt dried rockfish by sun and cold-air drying were 0.94 and 0.87, respectively, after three days of drying. Acid values (AV) were 10.71 and 5.96 mg KOH/g, respectively, after the three day drying period. The ADH activity in a water extract from salt dried rockfish following sun and cold-air drying for 24 h was 228.5% and 226.1% at 13.3 mg/mL, respectively, and was higher than that when drying lasted for 48 and 72 h. The ALDH activity was not affected but both ADH and ALDH activity tended to decrease as the drying time increased from 24 to 72 h. The conditions of processing for the best quality of salt dried rockfish were determined to be drying with a cold-air system for 24 h. These results indicated that water extracts from salt dried rockfish have valuable biological attributes owing to the metabolizing of alcohol and can provide useful information for the design of drying systems for salt dried rockfish.

Anti-inflammatory Effects of Black Cherry Tomato (Lycopersicon esculentum M.) Juice on LPS-induced RAW 264.7 Cells (LPS로 유도된 RAW 264.7 세포에 대한 흑색 방울토마토 주스의 항염증 효과)

  • Jung, Kyung Im;Ha, Nayeon;Choi, Young Ju
    • Journal of Life Science
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    • v.28 no.5
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    • pp.569-576
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    • 2018
  • This study was carried out to investigate the antioxidative, nitrite-scavenging, alcohol-metabolizing, and anti-inflammatory effects of black-cherry tomato juice (BCTJ) on LPS-induced RAW 264.7 cells. The total phenol content of the BCTJ was $156.83{\mu}g\;tannic-acid-equivalent/ml$. The antioxidative effects of BCTJ were measured using DPPH radical-scavenging activity and SOD-like assay. DPPH radical-scavenging activity of BCTJ was increased in a dose-dependent manner (p<0.05) and was 83.39% at 40%. SOD-like activity of BCTJ was 22.01% at 100%. The effects of BCTJ on alcohol-metabolism were determined by measuring generations of reduced nicotinamide adenine dinucleotides (NADH) by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). ADH and ALDH activities were 198.87% and 181.89% at 40%, respectively. Nitric scavenging activities of BCTJ were 85.06%, 58.25%, and 43.68% at pH values 1.2, 3.0, and 6.0, respectively, at 50%. Anti-inflammatory effects were examined in LPS-stimulated RAW 264.7 cells. Nitric-oxide production was reduced to 83.55% by the addition of BCTJ at 10%. These results suggest that black-cherry tomato juice has great potential as a resource for natural health products.