|Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart.|
|PMID: 18787169 Owner: NLM Status: MEDLINE|
|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.|
|Che-Hong Chen; Grant R Budas; Eric N Churchill; Marie-Hélène Disatnik; Thomas D Hurley; Daria Mochly-Rosen|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: Science (New York, N.Y.) Volume: 321 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2008 Sep|
|Created Date: 2008-09-12 Completed Date: 2008-09-25 Revised Date: 2014-09-09|
Medline Journal Info:
|Nlm Unique ID: 0404511 Medline TA: Science Country: United States|
|Languages: eng Pagination: 1493-5 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
antagonists & inhibitors,
Aldehydes / metabolism
Amino Acid Sequence
Benzamides / pharmacology*
Benzodioxoles / pharmacology*
Cardiotonic Agents / pharmacology*
Cyanamide / pharmacology
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
Protein Kinase C-epsilon / metabolism
|AA11147/AA/NIAAA NIH HHS; R01 AA011147/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|
|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; 3K9958V90M/Ethanol; 420-04-2/Cyanamide; EC 22.214.171.124/Aldehyde Dehydrogenase; EC 126.96.36.199/Aldh2 protein, rat; EC 188.8.131.52/Protein Kinase C-epsilon; G59M7S0WS3/Nitroglycerin|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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