title: Effect of the myosin light chain kinase inhibitor ML-7 on the proteome of hearts subjected to ischemia-reperfusion injury.
abstract: In the development of ischemia/reperfusion (I/R) injury, the role of the myosin light chain (MLC) phosphorylation has been given increased consideration. ML-7, a MLC kinase inhibitor, has been shown to protect cardiac function from I/R, however the exact mechanism remains unclear. Isolated rat hearts were perfused under aerobic conditions (controls) or subjected to I/R in the presence or absence of ML-7. Continuous administration of ML-7 (5 μM) from 10 min before onset of ischemia to the first 10 min of reperfusion resulted in significant recovery of heart contractility. Analysis of gels from two-dimensional electrophoresis revealed eight proteins with decreased levels in I/R hearts. Six proteins are involved in energy metabolism:ATP synthase beta subunit, cytochrome b-c1 complex subunit 1, 24-kDa mitochondrial NADH dehydrogenase, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, cytochrome c oxidase subunit, and succinyl-CoA ligase subunit. The other two proteins with decreased levels in I/R hearts are: peroxiredoxin-2 and tubulin. Administration of ML-7 increased level of succinyl-CoA ligase, key enzyme involved in the citric acid cycle. The increased level of succinyl-CoA ligase in I/R hearts perfused with ML-7 suggests that the cardioprotective effect of ML-7, at least partially, also may involve increase of energy production.
authors: Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Han-bin
authors: HB
authors: Lin
authors: Virgilio J J
authors: VJ
authors: Cadete
authors: Jolanta
authors: J
authors: Sawicka
authors: Mieczyslaw
authors: M
authors: Wozniak
authors: Grzegorz
authors: G
authors: Sawicki
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001696:Biomechanical Phenomena / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
chemical_list: D001381:Azepines; D002316:Cardiotonic Agents; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D020543:Proteome; C070571:ML 7; D009219:Myosin-Light-Chain Kinase