ArticleJournal of molecular and cellular cardiology2010
Activation of aldehyde dehydrogenase 2 (ALDH2) confers cardioprotection in protein kinase C epsilon (PKCvarepsilon) knockout mice.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Smoking, alcohol and opioids effect on coronary microcirculation: an update overview.BMC cardiovascular disorders · 2021Pooled it
- ALDH2 and ADH1 genetic polymorphisms may contribute to the risk of gastric cancer: a meta-analysis.PloS one · 2014Pooled it
- An Olive Oil-Based High-Fat Diet Promotes Obesity-Driven Metastasis of Triple-Negative Breast Cancer.Cancer research · 2025Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Cardioprotection Reloaded: Reflections on 40 Years of Research.Antioxidants (Basel, Switzerland) · 2025Review
- Advances in Factors Affecting ALDH2 Activity and its Mechanisms.Cardiovascular toxicology · 2024Review
- Healing the Ischaemic Heart: A Critical Review of Stem Cell Therapies.Reviews in cardiovascular medicine · 2023Review
- Accumulation of acetaldehyde in aldh2.1Redox biology · 2022Article
- Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention.International journal of molecular sciences · 2022Review
- Review
- Molecular Mechanism of HSF1-Upregulated ALDH2 by PKC in Ameliorating Pressure Overload-Induced Heart Failure in Mice.BioMed research international · 2020Article
- Aldehyde Dehydrogenase Inhibition Ameliorates Cardiac Dysfunction and Exacerbates Hypotension Caused by Alcohol in Female Rats.Alcoholism, clinical and experimental research · 2020Article
- Role of Alcohol Oxidative Metabolism in Its Cardiovascular and Autonomic Effects.Advances in experimental medicine and biology · 2019Review
- Ciliary neurotrophic factor stimulates cardioprotection and the proliferative activity in the adult zebrafish heart.NPJ Regenerative medicine · 2019Article
- Protein kinase Cε targets respiratory chain and mitochondrial membrane potential but not FJournal of cellular biochemistry · 2018Article
- Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury: An update.World journal of gastroenterology · 2018Review
- Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.Redox biology · 2018Article
- Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2.Cardiovascular research · 2018Article
- Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia.Redox biology · 2017Article
- Mitochondrial PKC-ε deficiency promotes I/R-mediated myocardial injury via GSK3β-dependent mitochondrial permeability transition pore opening.Journal of cellular and molecular medicine · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Acute administration of ethanol can reduce cardiac ischemia/reperfusion injury. Previous studies demonstrated that the acute cytoprotective effect of ethanol on the myocardium is mediated by protein kinase C epsilon (PKCvarepsilon). We recently identified aldehyde dehydrogenase 2 (ALDH2) as a PKCvarepsilon substrate, whose activation is necessary and sufficient to confer cardioprotection in vivo. ALDH2 metabolizes cytotoxic reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), which accumulate during cardiac ischemia/reperfusion. Here, we used a combination of PKCvarepsilon knockout mice and a direct activator of ALDH2, Alda-44, to further investigate the interplay between PKCvarepsilon and ALDH2 in cardioprotection. We report that ethanol preconditioning requires PKCvarepsilon, whereas direct activation of ALDH2 reduces infarct size in both wild type and PKCvarepsilon knockout hearts. Our data suggest that ALDH2 is downstream of PKCvarepsilon in ethanol preconditioning and that direct activation of ALDH2 can circumvent the requirement of PKCvarepsilon to induce cytoprotection. We also report that in addition to ALDH2 activation, Alda-44 prevents 4-HNE induced inactivation of ALDH2 by reducing the formation of 4-HNE-ALDH2 protein adducts. Thus, Alda-44 promotes metabolism of cytotoxic reactive aldehydes that accumulate in ischemic myocardium. Taken together, our findings suggest that direct activation of ALDH2 may represent a method of harnessing the cardioprotective effect of ethanol without the side effects associated with alcohol consumption.
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