Cardioprotective activity of a novel and potent competitive inhibitor of lactate dehydrogenase.
Alkaline incubation of NADH results in the formation of a very potent inhibitor of lactate dehydrogenase. High resolution mass spectroscopy along with NMR characterization clearly showed that the inhibitor is derived from attachment of a glycolic acid moiety to the 4-position of the dihydronicotinamide ring of NADH. The very potent inhibitor is competitive with respect to NADH. The inhibitor added in submicromolar concentrations to cardiomyocytes protects them from damage caused by hypoxia/reoxygenation stress. In isolated mouse hearts, addition of the inhibitor results in a substantial reduction of myocardial infarct size caused by global ischemia/reperfusion injury.
Kotlyar
Alexander B
AB
Molecular Biology Division, Veterans Affairs Medical Center, San Francisco, CA 94121, USA. s2shak@post.tau.ac.il
Randazzo
Antonio
A
Honbo
Norman
N
Jin
Zhu-Qui
ZQ
Karliner
Joel S
JS
Cecchini
Gary
G
D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D009206:Myocardium / Q000201:enzymology*; D009243:NAD / Q000737:chemistry / Q000494:pharmacology*
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D009243:NAD; D007770:L-Lactate Dehydrogenase