Редактирование: ALDH2

Aldehyde dehydrogenase, mitochondrial precursor (EC 1.2.1.3) (ALDH class 2) (ALDH-E2) (ALDHI) [ALDM]

==Publications==

{{medline-entry
|title=Aldehyde Dehydrogenase 2 ([[ALDH2]]) and Aging: Is There a Sensible Link?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31368109
|abstract=Aging is a complex irreversible biological process associated with increased prevalence of chronic disease and high healthcare burden. Several theories have been proposed for the biology of aging including free radical accumulation, DNA damage, apoptosis, telomere shortening, autophagy failure, and disturbed autonomic response. Aging is also closely associated with progressive deterioration of cardiovascular and neurological functions. Linkage, genome-wide association (GWAS), and next-generation sequencing analysis have confirmed a number of susceptibility loci for aging, in particular, Alzheimer's disease. Recent evidence from our group and others also revealed a tie between genetic mutation of mitochondrial aldehyde dehydrogenase ([[ALDH2]]) and life span as well as cardiovascular aging. [[ALDH2]] represents the single most gene with the greatest number of human genetic polymorphism and is deemed an important enzyme for detoxification of reactive aldehydes. Here, we will briefly review the tie between [[ALDH2]] and cardiovascular aging process. While recent work on [[ALDH2]] research has broadened the pathogenic mechanisms of [[ALDH2]] mutation or deficiency, therapeutic potential targeting [[ALDH2]] in the elderly still remains debatable.
|mesh-terms=* Aldehyde Dehydrogenase, Mitochondrial
* Cardiovascular System
* Genome-Wide Association Study
* Humans
* Longevity
* Polymorphism, Genetic
|keywords=* ALDH2
* Aging
* Autophagy
* Mitochondria
* Oxidative stress
|full-text-url=https://sci-hub.do/10.1007/978-981-13-6260-6_15
}}
{{medline-entry
|title=Appropriate dose of ethanol exerts anti-senescence and anti-atherosclerosis protective effects by activating [[ALDH2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30885430
|abstract=Moderate alcohol consumption has been shown to reduce atherosclerosis-associated diseases. As shown in our earlier works, ethanol has a dose-dependent protective effects against endothelial cellular senescence by activating aldehyde dehydrogenase 2 ([[ALDH2]]) in vitro. However, whether ethanol administration possesses anti-atherosclerosis properties and whether [[ALDH2]] is involved in the underlying mechanisms are unknown. In the present study, we revealed that the appropriate dose of ethanol reduced atherosclerotic plaque formation, and upregulated [[ALDH2]] expression and activity in ApoE  mice. [[ALDH2]] deficiency blocked the protection of ethanol against atherosclerotic plaque formation by inhibiting endothelium senescence. In contrast, Alda-1, which is a specific enzymatic agonist of [[ALDH2]], enhanced the anti-senescence and anti-atherosclerosis effects of the appropriate dose of ethanol. Furthermore, following [[ALDH2]] knockdown, resveratrol (an anti-aging compound) recovered the beneficial effects of ethanol against endothelial senescence in vitro. Thus, these results suggest that the appropriate dose of ethanol has protective effects against endothelial senescence and atherosclerosis by activating [[ALDH2]].
|mesh-terms=* Aldehyde Dehydrogenase, Mitochondrial
* Animals
* Atherosclerosis
* Benzamides
* Benzodioxoles
* Cardiotonic Agents
* Cells, Cultured
* Cellular Senescence
* Dose-Response Relationship, Drug
* Endothelium, Vascular
* Enzyme Activation
* Ethanol
* Gene Knockdown Techniques
* Humans
* Male
* Mice
* Mice, Knockout, ApoE
* RNA Interference
|keywords=* ALDH2
* Atherosclerosis
* Endothelial senescence
* Ethanol
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2019.03.037
}}
{{medline-entry
|title=Impaired enzymatic reactive aldehyde-detoxifying capacity and glutathione peroxidase activity in the aged human arterial tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30472277
|abstract=It is not known whether aging alters the enzymatic reactive aldehyde- and lipid hydroperoxide-detoxifying capacity of the human arterial tissue favoring vascular oxidative stress. To address this issue, we studied the specific enzymatic activities of class 1, 2 and 3 aldehyde dehydrogenase (ALDH1, [[ALDH2]] and ALDH3), glutathione S‑transferase (isozyme A4-4, [[GSTA4]]-4) and aldose reductase ([[AR]]), namely the major reactive aldehyde-scavenging enzymes, together with the activity of the lipid hydroperoxide-removing enzyme glutathione peroxidase (GSH-Px), in superior thyroid arteries (STA) specimens obtained in the thyroid surgery setting in aged subjects (age 72.3 ± 3.6 years) and young adult controls (age 31.9 ± 3.5 years). Vascular lipid peroxidation was also studied by assessing in STA fluorescent damage products of lipid peroxidation (FDPL), which reflect oxidant-induced 4‑hydroxynonenal and lipid hydroperoxide formation. Remarkably, the activities of ALDH1, [[ALDH2]], ALDH3, [[GSTA4]]-4, [[AR]] and GSH-Px were significantly lower, and FDPL levels higher, in the arterial tissue of the aged subjects than in that of the young adult controls. Moreover, the enzymatic activities were inversely and significantly correlated with the levels of FDPL in the arterial tissue of both the aged and young subjects, highlighting their vascular antioxidant/antilipoperoxidative role in vivo. Thus, aging impairs the enzymatic reactive aldehyde-detoxifying capacity and GSH-Px activity of the human arterial tissue eventually favoring vascular oxidative stress.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Aldehyde Dehydrogenase
* Aldehyde Reductase
* Arteries
* Case-Control Studies
* Female
* Glutathione Peroxidase
* Glutathione Transferase
* Humans
* Lipid Peroxidation
* Male
* Oxidative Stress
|keywords=* Aging
* Aldehyde dehydrogenase
* Aldose reductase
* Glutathione S‑transferase
* Glutathione peroxidase
* Lipid peroxidation
* Oxidative stress
* Reactive aldehydes
|full-text-url=https://sci-hub.do/10.1016/j.exger.2018.11.013
}}
{{medline-entry
|title=Telomere shortening in alcohol dependence: Roles of alcohol and acetaldehyde.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30466069
|abstract=Heavy drinking leads to premature aging and precipitates the onset of age-related diseases. Acetaldehyde (AcH), a toxic metabolite of ethanol, has been implicated in various types of cancer. However, whether alcohol accelerates biological aging at a cellular level is controversial and the mechanism involved is unclear. We addressed these questions by measuring telomere length (TL) in peripheral blood leukocytes of Japanese patients with alcohol dependence (AD) and examined the association between TL, genetic variants of alcohol dehydrogenase (ADH)1B and aldehyde dehydrogenase (ALDH)2, and other clinical characteristics. A total of 134 male AD patients and 121 age- and sex-matched healthy controls were evaluated. All patients received endoscopic screening for cancer of the upper aerodigestive tract (UADT). TL was almost 50% shorter in AD patients relative to controls. There were no significant differences in TL between AD patients with and without UADT cancer, and no associations between [[ADH1B]] and [[ALDH2]] genotypes and TL. AD patients with thiamine (vitamin B1) deficiency at admission had significantly shorter TL than those with normal thiamine status. Although the exact mechanism underlying the shorter TL in AD patients remain unclear, our findings suggest that alcohol rather than AcH is associated with telomere shortening in AD, which may be accelerated by thiamine deficiency. Future studies should also focus on the association between telomere shortening and TD in the context of oxidative stress.
|mesh-terms=* Acetaldehyde
* Aged
* Aging, Premature
* Alcoholism
* Aldehyde Dehydrogenase, Mitochondrial
* Ethanol
* Humans
* Japan
* Male
* Middle Aged
* Telomere Shortening
* Thiamine Deficiency
|keywords=* ALDH2
* Age-related disease
* Alcohol dependence
* Premature aging
* Telomere length
* Thiamine/vitamin B1 deficiency
|full-text-url=https://sci-hub.do/10.1016/j.jpsychires.2018.11.007
}}
{{medline-entry
|title=Aldehyde dehydrogenase 2 deficiency promotes atherosclerotic plaque instability through accelerating mitochondrial ROS-mediated vascular smooth muscle cell senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30315930
|abstract=Previous evidence has indicated a beneficial role for aldehyde dehydrogenase 2 ([[ALDH2]]) in suppressing atherosclerotic plaque progression and instability. However, the underlying mechanism remains somewhat elusive. This study was designed to examine the effect of [[ALDH2]] deficiency on high-cholesterol diet-induced atherosclerotic plaque progression and plaque vulnerability in atherosclerosis-prone ApoE knockout (ApoE ) mice with a focus on foam cell formation in macrophages and senescence of vascular smooth muscle cells (VSMCs). Serum lipid profile, plaque progression, and plaque vulnerability were examined in ApoE  and [[ALDH2]]/ApoE double knockout ([[ALDH2]] ApoE ) mice after high-cholesterol diet intake for 8 weeks. [[ALDH2]] deficiency increased the serum levels of triglycerides while it decreased levels of total cholesterol and high-density lipoprotein cholesterol. Unexpectedly, [[ALDH2]] deficiency reduced the plaque area by 58.9% and 37.5% in aorta and aortic sinus, respectively. Plaque instability was aggravated by [[ALDH2]] deficiency along with the increased necrotic core size, decreased collagen content, thinner fibrous cap area, decreased VSMC content, and increased macrophage content. In atherosclerotic lesions, [[ALDH2]] protein was located in both macrophages and VSMCs. Further results revealed downregulated [[ALDH2]] expression in aorta of aged ApoE  mice compared with young mice. However, in vitro study suggested that [[ALDH2]] expression was upregulated in bone marrow-derived macrophages (BMDMs) with an opposite effect in VSMCs following 80 μg/ml oxidized low-density lipoprotein (oxLDL) treatment. Interestingly, [[ALDH2]] deficiency displayed little effect in oxLDL-induced foam cell formation from BMDMs, while [[ALDH2]] knockdown by siRNA and [[ALDH2]] overexpression by lentivirus infection promoted and retarded oxLDL-induced VSMC senescence, respectively. Mechanistically, [[ALDH2]] mitigated oxLDL-induced overproduction of mitochondrial reactive oxygen species (mROS) and activation of downstream p53/p21/p16 pathway. Clearance of mROS by mitoTEMPO significantly reversed the promotive effect of [[ALDH2]] knockdown on VSMC senescence. Taken together, our data revealed that [[ALDH2]] deficiency suppressed atherosclerotic plaque area while facilitating plaque instability possibly through accelerating mROS-mediated VSMC senescence. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren