Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart.
Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart.
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DOI：
10.1126/science.1158554
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发表时间：
2008-09-12
期刊：
影响因子：
--
通讯作者：
Mochly-Rosen D
中科院分区：
文献类型：
--
作者：
Chen CH;Budas GR;Churchill EN;Disatnik MH;Hurley TD;Mochly-Rosen D
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 an unbiased proteomic search 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 prior to 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 wildtype or mutant ALDH2 subjected to cardiac ischemia, such as during coronary bypass surgery. (140/140 words)
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DOI：
10.1073/pnas.95.2.510
发表时间：
1998-01-20
影响因子：
11.1
作者：
Lucas, DT;Szweda, LI
通讯作者：
Szweda, LI
影响因子：
4.1
作者：
Doorn, JA;Hurley, TD;Petersen, DR
通讯作者：
Petersen, DR
DOI：
10.1073/pnas.0503723102
发表时间：
2005-08-23
影响因子：
11.1
作者：
Chen, ZQ;Foster, MW;Stamler, JS
通讯作者：
Stamler, JS
DOI：
10.1073/pnas.81.13.4055
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DUESTER, G;HATFIELD, GW;SMITH, M
通讯作者：
SMITH, M
影响因子：
37.8
作者：
Hill, M;Takano, H;Bolli, R
通讯作者：
Bolli, R