Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart.
Science
; 321(5895): 1493-5, 2008 Sep 12.
Article
em En
| MEDLINE
| ID: mdl-18787169
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
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Cardiotônicos
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Traumatismo por Reperfusão Miocárdica
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Proteínas Mitocondriais
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Aldeído Desidrogenase
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Benzodioxóis
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Infarto do Miocárdio
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Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos