PMID:18787169

Citation	Chen, CH, Budas, GR, Churchill, EN, Disatnik, MH, Hurley, TD and Mochly-Rosen, D (2008) Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 321:1493-5
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.
Links	PubMed PMC2741612 Online version:10.1126/science.1158554
Keywords	Aldehyde Dehydrogenase/antagonists & inhibitors; Aldehyde Dehydrogenase/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; Mitochondrial Proteins/antagonists & inhibitors; Mitochondrial Proteins/metabolism; Molecular Sequence Data; Myocardial Infarction/enzymology; Myocardial Infarction/pathology; Myocardial Infarction/prevention & control; Myocardial Reperfusion Injury/enzymology; Myocardium/enzymology; Myocardium/pathology; Nitroglycerin/pharmacology; Phosphorylation; Protein Kinase C-epsilon/metabolism; Proteomics; Rats; Rats, Wistar
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:ALDH2		GO:0004029: aldehyde dehydrogenase (NAD) activity	ECO:0000315:		F		Figure 2 shows that ALDH2 activity increases in the presence of AldA-1	complete CACAO 2544
RAT:ALDH2	enables	GO:0004029: aldehyde dehydrogenase (NAD) activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.