• 생물정신의학
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• 제12권2호
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• pp.196-206
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• 2005

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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2973-2978
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• 2012

Background: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

• 한국식품영양학회지
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• 제10권2호
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• pp.268-271
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• 1997

사람의 미토콘드리아에 있는 aldehyde dehydrogenase(ALDH2)는 체내에서 알코올 대사 과정 중에 생성되는 아세트알데히드를 산화시키는 주된 역할을 담당하고 있다. 이 ALDH2가 알코올 대사에 미치는 영향을 연구하기 위하여 가용화된 효소가 필요하다. 알려져 있는 유전자의 염기서열 데이터를 바탕으로 ALDH2의 cDNA는 cDNA 라이브러리에서 선별하였으며, 이를 여러 가지 대장균 발현벡터에 연결하였다. 제조한 발현벡터를 형질전환시킨 대장균을 사용하여 단백질의 발현을 확인한 결과 대부분의 계에서 ALDH가 과발현되고 있었다. 그러나 발현된 단백질의 대부분은 inclusion body로 형성되어, 실제로 가용화된 효소의 양은 전체 발현된 양의 5% 이하 였고 이들 몇 가지 발현 system으로 재조합 미오2DML 발현을 확인하였다.

• International Journal of Oral Biology
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• 제31권3호
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• pp.107-112
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• 2006

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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7491-7496
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• 2015

Background: Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We investigated the possible correlation between cancer stem cell (CSC) markers (CD133, and ALDH1) in invasive ductal breast carcinomas with some clinicopathological parameters. Aim: To assess the correlation between expression of cancer stem cell (CSC) markers (CD133, and ALDH1) and clinicopathological parameters of invasive ductal breast carcinomas. Materials and Methods: Immunohistochemical analysis of CD133 and ALDH1 was performed on a series of 120 modified radical mastectomy (MRM) specimens diagnosed as invasive ductal breast carcinoma. Results: Expression of both CD133 and ALDH1 was significantly changed and related to tumor size, tumor stage (TNM), and lymph node metastasis. A negative correlation between CD133 and ALDH1 was found. Conclusions: Detecting the expression of CD133 and ALDH1 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties and determining the optimal treatment.

• 대한의생명과학회지
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• 제14권1호
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• pp.13-18
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• 2008

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. Individuals who regularly consume excessive quantities of alcohol have a greater risk of developing head and neck cancers such as esophageal, pharyngeal and oral cavity cancers if they are deficient in ALDH2 expression compared to normal populations. We evaluated lipid peroxidation in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Malondialdehyde(MDA) level in liver tissue was evaluated as a biomarker of oxidative lipid peroxidation. Although the ethanol treatment did not increase the hepatic MDA level both in Aldh2 +/+ mice and in Aldh2 -/- mice, the MDA level was significant higher in the Aldh2 -/- mice than in the Aldh2 +/+ group. The MDA level was also significantly correlated with olive tail moment in blood and the level of 8-OHdG in liver tissue. This is a strong evidence to support our hypothesis that oxidative stress is more intense in Aldh2 -/- mice than in Aldh2 +/+ mice. Our results suggest that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.

• 생물정신의학
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• 제31권1호
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• pp.1-6
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• 2024

Objectives Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase enzyme in the liver and then acetaldehyde is metabolized to acetone by aldehyde dehydrogenase (ALDH) in the liver. There are two main ALDH enzymes which metabolize the acetaldehyde produced during ethanol oxidation. In particular, in the presence of the ALDH2 1^*2 allele, the activity of the ALDH 2 enzyme is lowered. As a result, acetaldehyde metabolism is slowed down and acetaldehyde accumulates in the body compared to the ALDH2 1^*1 allele. There are many studies that have investigated the blood acetaldehyde concentration according to the ALDH2 genotype, but there are few studies to compare this with age. So we investigated the blood acetaldehyde concentration according to ALDH2 genotype, age and gender. Methods According to the ALDH2 genotype, we divided the group by gender and age. We divided the age group in to three groups which ranged from 20 to 34 years old, from 35 to 49 years old, and lastly from 50 to 64 years old. And then we collected blood samples after 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr and 15 hr of after drinking to measure the blood acetaldehyde concentration. Results In ALDH2 1^*2 allele group, there are significant differences of the blood acetaldehyde concentration between the age groups. In ALDH2 1^*2 allele and male group, there are significant differences of the blood acetaldehyde concentration between the age groups. Conclusions There are significant differences of the blood acetaldehyde concentration between the age groups according to ALDH2 genotype. Also, there are significant differences of the blood acetaldehyde concentration between the age groups with male gender and ALDH2 1^*2 allele. Studies about other factors that may influence the blood acetaldehyde concentration are needed.

• International Journal of Stem Cells
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• 제17권3호
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• pp.284-297
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• 2024

Acetaldehyde dehydrogenase 2 (ALDH2) is the second enzyme involved in the breakdown of acetaldehyde into acetic acid during the process of alcohol metabolism. Roughly 40% of East Asians carry one or two ALDH2^*2 alleles, and the presence of ALDH2 genetic mutations in individuals may affect the bone remodeling cycle owing to accumulation of acetaldehyde in the body. In this study, we investigated the effects of ALDH2 mutations on bone remodeling. In this study, we examined the effects of ALDH2 polymorphisms on in vitro osteogensis using human induced pluripotent stem cells (hiPSCs). We differentiated wild-type (ALDH2^*1/^*1-) and ALDH2^*1/^*2-genotyped hiPSCs into osteoblasts (OBs) and confirmed their OB characteristics. Acetaldehyde was administered to confirm the impact caused by the mutation during OB differentiation. Calcium deposits formed during osteogenesis were significantly decreased in ALDH2^*1/^*2 OBs. The expression of osteogenic markers were also decreased in acetaldehyde-treated OBs differentiated from the ALDH2^*1/^*2 hiPSCs. Furthermore, the impact of ALDH2 polymorphism and acetaldehyde-induced stress on inflammatory factors such as 4-hydroxynonenal and tumor necrosis factor α was confirmed. Our findings suggest that individuals with ALDH2 deficiency may face challenges in acetaldehyde breakdown, rendering them susceptible to disturbances in normal bone remodeling therefore, caution should be exercised regarding alcohol consumption. In this proof-of-concept study, we were able to suggest these findings as a result of a disease-in-a-dish concept using hiPSCs derived from individuals bearing a certain mutation. This study also shows the potential of patient-derived hiPSCs for disease modeling with a specific condition.

• Journal of Microbiology
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• 제37권1호
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• pp.41-44
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• 1999

Human mitochondrial aldehyde dehydrogenase 2 (ALDH2) is mainly responsible for oxidation of acetaldehyde generated during alcohol oxidation in vivo. A full-length cDNA of human liver ALDH2 was successfully expressed using a vaccinia virus-T7 RNA polymerase system. The expressed ALDH2 had an enzymatic activity as high as the native human liver ALDH2 enzyme.

• 생명과학회지
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• 제18권8호
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• pp.1173-1176
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• 2008

본 연구에서는 ALDH2 knockout 마우스를 이용하여 에탄올을 경구 투여한 후 간조직 및 뇌조직, 그리고 폐조직에서의 8-hydroxydeoxyguanosine (8-OHdG) 농도를 측정하여 각 장기에서의 산화적 유전자 손상정도를 평가하고 ALDH2 효소활성과의 관련성을 파악하였다. 간조직의 8-OHdG 농도는 에탄올 투여에 의해서도 유의하게 증가하지만 ALDH2 효소의 결핍이 더욱 큰 영향을 주는 것으로 확인되었다. 또한, 뇌조직과 폐조직의 8-OHdG 농도도 에탄올에 의해 모두 유의하게 증가하는 것으로 나타났으며 폐조직에서의 8-OHdG 농도는 ALDH2 효소의 활성에 따라 유의하게 영향을 받는 것으로 나타났다. 본 연구에서 에탄올의 반복적인 투여는 간조직 뿐 아니라 뇌조직과 폐조직에서도 산화적 유전자 손상을 유발하는 것으로 확인되었으며, 적어도 에탄올에 의한 간조직과 폐조직에서의 산화적 유전자 손상은 ALDH2 활성이 결핍된 경우에 더욱 커지는 것으로 조사되었다. 본 연구의 결과는 ALDH2 효소가 결핍된 사람에서 각종 암발생 위험도가 크게 나타나는 이유를 규명하는데 매우 중요한 근거자료로 활용될 수 있을 것으로 기대된다.