| Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. | |
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MedLine Citation:
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PMID: 18787169 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures. Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations. Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as during coronary bypass surgery. |
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Authors:
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Che-Hong Chen; Grant R Budas; Eric N Churchill; Marie-Hélène Disatnik; Thomas D Hurley; Daria Mochly-Rosen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 321 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-12 Completed Date: 2008-09-25 Revised Date: 2010-08-17 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1493-5 Citation Subset: IM |
Affiliation:
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Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldehyde Dehydrogenase
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antagonists & inhibitors,
metabolism* Aldehydes / metabolism Amino Acid Sequence Animals Benzamides / pharmacology* Benzodioxoles / pharmacology* Cardiotonic Agents / pharmacology* Cyanamide / pharmacology Enzyme Activation Ethanol / pharmacology Ischemic Preconditioning, Myocardial Mitochondrial Proteins / agonists, antagonists & inhibitors, metabolism* Molecular Sequence Data Myocardial Infarction / enzymology, pathology, prevention & control* Myocardial Reperfusion Injury / enzymology* Myocardium / enzymology*, pathology Nitroglycerin / pharmacology Phosphorylation Protein Kinase C-epsilon / metabolism Proteomics Rats Rats, Wistar |
| Grant Support | |
ID/Acronym/Agency:
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AA11147/AA/NIAAA NIH HHS; R01 AA011147-08/AA/NIAAA NIH HHS; R01 AA011147-09/AA/NIAAA NIH HHS; R01 AA011147-10/AA/NIAAA NIH HHS; R01 AA011147-11/AA/NIAAA NIH HHS; R01 AA011147-12/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 0/Benzamides; 0/Benzodioxoles; 0/Cardiotonic Agents; 0/Mitochondrial Proteins; 0/N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; 29343-52-0/4-hydroxy-2-nonenal; 420-04-2/Cyanamide; 55-63-0/Nitroglycerin; 64-17-5/Ethanol; EC 1.2.1.3/Aldehyde Dehydrogenase; EC 1.2.1.3/Aldh2 protein, rat; EC 2.7.11.13/Protein Kinase C-epsilon |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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