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Facts about Aldehyde dehydrogenase, mitochondrial.
Human | |
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Gene Name: | ALDH2 |
Uniprot: | P05091 |
Entrez: | 217 |
Belongs to: |
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aldehyde dehydrogenase family |
acetaldehyde dehydrogenase 2; aldehyde dehydrogenase 2 family (mitochondrial); aldehyde dehydrogenase, mitochondrial; ALDH class 2; ALDH2; ALDH-E2; ALDHI; ALDM; EC 1.2.1; EC 1.2.1.3; liver mitochondrial ALDH; MGC1806; nucleus-encoded mitochondrial aldehyde dehydrogenase 2
Mass (kDA):
56.381 kDA
Human | |
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Location: | 12q24.12 |
Sequence: | 12; NC_000012.12 (111766933..111817532) |
Mitochondrion matrix.
ALDH2 is a versatile enzyme that is a vital part of the human body. It is found in the myocardium, liver, as well as cancer cells. But what are its most effective uses? Find out more about its application in research. Find out how it is found in human cancer cells. This article will discuss the most popular uses for the ALDH2 marker.
ALDH2 dehydrogenase has many functions in the contexts of cardiovascular disease (CVD). ALDH2 converts ethanol-derived acetaldehyde into acetate and is a potent inhibitor of the peroxidation of lipids. Its inactive variant has been linked to increased cholesterol in certain populations and has been implicated as a risk factor for cardiovascular disease. Additionally, it interacts with AMPK and LDLR and regulates foam cell formation in macrophages.
ALDH2 plays an important role in protecting the liver from IRI through regulation of autophagy. The liver tissues were stained by immunofluorescence for P62 and LC3B as measured by Western blot. Transmission electron micrographs of representative samples also revealed that autophagosomes are present within the cytoplasm of 100 mm2 ischemic liver tissue. After Alda-1 treatment mice were treated with 3-methyladenine and killed within six hours.
The evidence from molecular studies suggests that ALDH2 functions at the mitochondrial level, by interfering with HMGCR. HMGCR interaction may lead to improved survival and the regeneration of your heart. ALDH2 also regulates cholesterol synthesis through blocking the cytosolic JNK/p53 process. This pathway is involved in the suppression and production of hepatic cholesterol through ALDH2.
Higher levels of cholesterol were detected in mice with the genetic variant ALDH2RS671, which is closely related to the liver enzyme HMGCR. The detection of ALDH2 in human hepatocytes reveals an important link between ALDH2 expression and the development of cardiovascular disease (CVD).
ALDH2 activities in human hepatocytes have been determined using an ALDH2 activity assay kit. The results were expressed as nmol/min per mg protein. In a second study, ALDH2 activity was associated with decreased levels of malondialdehyde (H2O2) in human liver tissues. ALDH2 expression isn't believed to be directly affected by GTN. However H2 treatment has produced significant effects on cancerous cells and suggests it could play an important role in the process of regenerating the lung.
The administration of CCl4 raised levels H3K24me3, HO-1 , and Bax in the livers of mice. The ALDH2 knockout mice also showed elevated ROS, and reduced Bax and Bcl-2. This suggests that ALDH2 activation could reduce the hepatic inflammation caused by CCl4. However, the knockout mice were not affected by CCl4 administration. Their livers had a more granular and rougher surface.
ALDH2 is involved in de novo cholesterol synthesis in the liver. Over-expression of ALDH2 can hinder the absorption of cholesterol. The gene can also be knocked down to lower cholesterol levels. Over-expression of ALDH2 reverses the TGF-b1 effects in living. Alda-1 administration protects livers from fibrosis in mice. However the treatment with lovastatin has been observed in ALDH2 knockdown mice to reduce cholesterol levels.
The metabolism of the brain can be affected by ALDH2. It isn't known whether ALDH2 is involved in the effects of alcohol on behavior. Li Zhang and his colleagues recently studied the cell-specific expression ALDH2 in cerebellum. This region is important for balance and posture. ALDH2 also was found in the astrocytes which are cells of the glial family that play a role in motor coordination.
The detection of ALDH2 in the human myocardium is important to assess the functional significance of the enzyme in the cardiac muscle. In diabetic patients, ALDH2 activity is decreased. Hyperglycemia lowers ALDH2 activity by almost half. The enzyme's activity is in inverse correlation with the O-GlcNAc modifications it undergoes. Hyperglycemia can also increase ALDH2 O-GlcNAc modifications.
The role of ALDH2 in cardiac protection is unclear, but studies indicate that this enzyme has an important role to play in cardiac protection. ALDH2 has been shown to play a crucial role in protecting cardiac cells from ischemic injury in the human myocardium. ALDH2 could also play an important role in cardioprotection after H/R injury.
To measure the activity of ALDH2 in the human myocardium mitochondria were removed from human myocardial tissues or cardiomyocytes using a Beyotime Mitochondria Isolation Kit. After the mitochondria were isolated, they were subsequently centrifuged at 11,000xg for 10 min at 4degC. ALDH2 activity was determined by measuring the absorbance at 354 nm using a Beckman instrument and a kinetics module.
The decreased activity of ALDH2 was also evident during the development of HF following MI. Loss of ALDH2 function caused cardiomyocyte apoptosis and prevented the development of HF. ALDH2 is responsible for detoxifying 4-HNE, a mediator of programmed cell death. ALDH2 transmits the ALDH2 signal from mitochondria to the cytosol, activating the JNK/p53 pathway.
After Adenovirus vectors encoding ALDH2 were infected into the myocardium of wild-type mice it was found that apoptotic tissues were present in the noninfarction zone. ALDH2-KO hearts had smaller infarcts and had more cardiomyocytes positive for TUNEL than wild-type mice. These results were presented as the average plus SEM of five mice.
A gene polymorphism in ALDH2 has been discovered in the human molecular genetics. It is associated with lower FEV1/FVC. ALDH2 has an lower rate of colony formation and this suggests that this polymorphism may be linked to lung ageing. This gene plays a significant role in the biotransformation of GTN. This condition can be prevented or reversed by transfection of ALDH2.
A recent study has shown that ALDH2 can also decrease the O-GlcNAc levels in the human myocardium. This gene was cloned by human peripheral blood mononuclear cell clones. It is a homotetramer and contains three subunits. Each subunit has three main domains. The Alda-1 binding location is located in the substrate entrance tunnel of ALDH2 which is located on the surface.
Researchers will be able to determine the gene responsible for ADH regulation by the detection of ALDH2 in human myocardium. The protein is essential to ensure proper lysis of acetaldehyde, a byproduct of alcohol metabolism. However this gene is extensively expressed in Asian and East Asian populations. This means that the polymorphism could be a major factor in the cause of alcoholic heart disease.
The detection of ALDH2 is an important indicator for cancer stem cells (CSC). The expression of this gene is linked to various oncogenic pathways such as cell proliferation, cell growth, and the immune system. While the exact mechanism behind this is not known, it is believed that it contributes to the lower survival rate for colorectal cancers than other kinds. Here are some examples showing tumor cells with high levels of ALDH2 expression.
Detection of ALDH2 in HNSC patients correlates with good prognosis. However age, stage and age are also important factors that influence the survival of patients. HNSC tumors with high levels of ALDH2 are more likely to recur than cancer cells with high levels.
Activation of ALDH2 in cancer cells is an important part of the chemopreventive strategy for patients suffering from cancer with ALDH2*2 mutations. ALDH activators can reduce the likelihood of cancer recurrence and second-degree tumors. Patients with high risk profiles might be able to stay clear of alcohol by activating ALDH2 in their cancerous cells.
ALDh2 and ALDH2 are similar in controlling DNA repair networks. They are also referred to as aldehyde-dehydrogenase and can be found in all eukaryotic cells, including the leukemia clone, L1210 and the cornea as well as a variety of types of cancer. This enzyme is involved in the formation of retinoid, as well as in regulating the retinoid signal.
The TCGA pan-cancer database shows that ALDH2 is present in both normal and tumor tissue. ALDH2 was significantly decreased in 91 HNSC compared to 23 normal tissues. ALDH2 expression was detected in three different datasets: TCGA, paired normal tissue, and ROC curves. The results are encouraging even however the data were not enough to prove the link.
In a recent study researchers from the University of California San Diego and the University of Illinois at Chicago Medical School discovered that the ALDH2 gene was associated with poor outcomes for patients suffering from hepatocellular cancer. The study also revealed that ALDh2A1 was associated to poor prognosis for patients suffering from nonsmall-cell lung cancer that is in its early stages. Additionally, ALDh2A1 in combination with CD133 were discovered to be linked to the expression of cancer stem cells.
These findings are significant because the polymorphism of ALDH2 is strongly linked with cancer risk. Programs that encourage alcohol consumption reduction and cessation could include screening for the ALDH2*2 variant. In the future, the findings could be used to develop an assessment of risk which targets ALDH2-deficient persons for alcohol-related cancers. ALDH2 polymorphism screening should not be performed until after that.
Recent research has linked ALDH2 activity in the bone to tumor cells, and high levels of ALDH2 expression in these cells. This gene is located in the mucosa layer of the basal. The presence of this gene in tumor cells suggests that cancer stem-like cells originate from normal mucosa. Since it is common in cancer cells, it is essential to understand the role it plays in cancer.
PMID: 3582651 by Braun T., et al. Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase.
PMID: 3562250 by Braun T., et al. Isolation and sequence analysis of a full length cDNA clone coding for human mitochondrial aldehyde dehydrogenase.
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