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.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Lin HB,Cadete VJ,Sawicka J,Wozniak M,Sawicki G

doi

10.1016/j.jprot.2012.06.016

subject

Has Abstract

pub_date

2012-09-18 00:00:00

pages

5386-95

issue

17

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(12)00477-0

journal_volume

75

pub_type

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