Long-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway

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dc.contributor.authorEngelbrecht A.-M.
dc.contributor.authorEngelbrecht P.
dc.contributor.authorGenade S.
dc.contributor.authorNiesler C.
dc.contributor.authorPage C.
dc.contributor.authorSmuts M.
dc.contributor.authorLochner A.
dc.date.accessioned2011-05-15T15:59:43Z
dc.date.available2011-05-15T15:59:43Z
dc.date.issued2005
dc.description.abstractThe mechanisms by which long-chain dietary polyunsaturated fatty acids (PUFAs) protect against cardiovascular disease are largely unknown. The present study determines the effects of eicosapentaenoic acid (EPA) and arachidonic acid (ARA) on the response of neonatal rat cardiomyocytes to simulated ischaemia (SI) and reperfusion (R). Myocytes isolated from 1-2 day old Wistar rat hearts were cultured with or without EPA or ARA and exposed to 1 h SI followed by 30 minutes reperfusion. Apoptosis was evaluated by caspase-3 activation, poly-(ADP-ribose) polymerase (PARP) cleavage and nuclear condensation. EPA (20μM) and ARA (20μM) significantly inhibited caspase-3 activation and PARP-cleavage and reduced the apoptotic index during reperfusion. Both fatty acids significantly increased ERK phosphorylation and decreased p38 phosphorylation during reperfusion. The mechanism of action of ARA on the MAPKs was further investigated with okadaic acid (to inhibit serine-threonine phosphatases) and orthovanadate (to inhibit tyrosine phosphatases). Vanadate, but not okadaic acid, significantly reduced ARA-induced inhibition of p38 phosphorylation, suggesting the involvement a tyrosine phosphatase during SI/R. Mitogen-activated protein kinase phosphatase-1 (MKP-1), a dual-specificity phosphatase, was targeted and a significant induction of MKP-1 by ARA and EPA was observed. It was demonstrated for the first time that EPA and ARA protect neonatal cardiac myocytes from ischaemia/reperfusion-induced apoptosis through activation of ERK as well as induction of a dual-specific phosphatase, causing dephosphorylation of the pro-apoptotic kinase, p38. The cardioprotective effects of EPA and ARA could also be demonstrated on the functional recovery of isolated perfused hearts subjected to global ischemia. © 2005 Elsevier Ltd. All rights reserved.
dc.description.versionArticle
dc.identifier.citationJournal of Molecular and Cellular Cardiology
dc.identifier.citation39
dc.identifier.citation6
dc.identifier.issn222828
dc.identifier.other10.1016/j.yjmcc.2005.08.004
dc.identifier.urihttp://hdl.handle.net/10019.1/11325
dc.subjectarachidonic acid
dc.subjectcaspase 3
dc.subjecticosapentaenoic acid
dc.subjectmitogen activated protein kinase
dc.subjectnicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
dc.subjectokadaic acid
dc.subjectorthovanadic acid
dc.subjectphosphatase
dc.subjectpolyunsaturated fatty acid
dc.subjectsynaptophysin
dc.subjectanimal cell
dc.subjectanimal model
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcell isolation
dc.subjectcell viability
dc.subjectcontrolled study
dc.subjectdephosphorylation
dc.subjectdrug effect
dc.subjectdrug mechanism
dc.subjectenzyme activation
dc.subjectenzyme degradation
dc.subjectenzyme inhibition
dc.subjectenzyme phosphorylation
dc.subjectenzyme specificity
dc.subjectfatty acid analysis
dc.subjectheart muscle cell
dc.subjectheart muscle ischemia
dc.subjectheart protection
dc.subjectmuscle fiber culture
dc.subjectnewborn
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectrat
dc.subjectreperfusion injury
dc.subjectsignal transduction
dc.subjectAnimals
dc.subjectAnimals, Newborn
dc.subjectApoptosis
dc.subjectArachidonic Acid
dc.subjectCells, Cultured
dc.subjectEicosapentaenoic Acid
dc.subjectMAP Kinase Signaling System
dc.subjectMyocardial Reperfusion Injury
dc.subjectMyocardium
dc.subjectMyocytes, Cardiac
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectAnimalia
dc.subjectRattus norvegicus
dc.titleLong-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway
dc.typeArticle
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