Topic
Aldehyde dehydrogenase
About: Aldehyde dehydrogenase is a research topic. Over the lifetime, 3365 publications have been published within this topic receiving 107683 citations.
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TL;DR: Preliminary evidence is provided that treatment with the novel cell population, ALDH(br) cells, is safe and may provide perfusion and functional benefits in patients with chronic myocardial ischemia.
89 citations
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TL;DR: The large interethnic and interindividual variability in alcohol-induced toxic effects comes from a combination of genetic and environmental factors, influencing ethanol toxicokinetics.
Abstract: The large interethnic and interindividual variability in alcohol-induced toxic effects comes from a combination of genetic and environmental factors, influencing ethanol toxicokinetics. The hepatic enzymatic systems involved in ethanol metabolism are alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal P4502E1 (CYP2E1). ADH oxidizes ethanol to acetaldehyde, which is very efficiently oxidized to acetate by ALDH. About 10% of moderate quantities of ethanol is metabolised by CYP2E1; the percentage increases when ADH is saturated. During ethanol metabolism reactive oxygen species and hydroxyethyl radicals are generated, causing oxidative stress, responsible for most ethanol-induced liver damage. For their critical role in detoxifying radicals, glutathione S-transferase are gaining attention in the etiology of alcoholism. All these enzymes have been shown to be polymorphic, giving rise to altered phenotypes. For this reason recent studies have looked for a correlation between metabolic variability and differences in alcohol abuse-related effects.
88 citations
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TL;DR: It is established that AL DH2 controls cell survival decisions by modulating oxidative stress levels and that this regulatory circuitry was dysfunctional in the loss-of-function ALDH2*2 genotype, causing up-regulation of apoptosis in cardiomyocytes after ischemic insult.
Abstract: Nearly 8% of the human population carries an inactivating point mutation in the gene that encodes the cardioprotective enzyme aldehyde dehydrogenase 2 (ALDH2). This genetic polymorphism (ALDH2*2) is linked to more severe outcomes from ischemic heart damage and an increased risk of coronary artery disease (CAD), but the underlying molecular bases are unknown. We investigated the ALDH2*2 mechanisms in a human model system of induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation gave rise to elevated amounts of reactive oxygen species and toxic aldehydes, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. We established that ALDH2 controls cell survival decisions by modulating oxidative stress levels and that this regulatory circuitry was dysfunctional in the loss-of-function ALDH2*2 genotype, causing up-regulation of apoptosis in cardiomyocytes after ischemic insult. These results reveal a new function for the metabolic enzyme ALDH2 in modulation of cell survival decisions. Insight into the molecular mechanisms that mediate ALDH2*2-related increased ischemic damage is important for the development of specific diagnostic methods and improved risk management of CAD and may lead to patient-specific cardiac therapies.
88 citations
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TL;DR: The present results indicate that acetaldehyde is metabolized within human lymphocytes, and that alcohol consumption during treatment with drugs that inactivate aldehyde dehydrogenase may cause a further increased incidence of acetaldehyde-induced SCE and concomitant lesions.
88 citations
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TL;DR: Results indicate that lysine 262 in aldose reduct enzyme and aldehyde reductase is crucial to their catalytic activity by affecting co-factor binding.
88 citations