Activation of p38 MAPK induced by a multi-cycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion

Simple item page
dc.contributor.authorMarais E.
dc.contributor.authorGenade S.
dc.contributor.authorHuisamen B.
dc.contributor.authorStrijdom J.G.
dc.contributor.authorMoolman J.A.
dc.contributor.authorLochner A.
dc.date.accessioned2011-05-15T15:59:43Z
dc.date.available2011-05-15T15:59:43Z
dc.date.issued2001
dc.description.abstractThe role of p38 mitogen-activated protein kinase (MAPK) in ischaemic preconditioning remains controversial. Since most previous studies focussed on events only during sustained ischaemia, the aim of this study was to establish the activation pattern of p38 MAPK during a multicycle preconditioning protocol, sustained ischaemia as well as reperfusion and to correlate these events with functional recovery of the isolated perfused rat heart. Isolated perfused rat hearts were preconditioned by 3 × 5 min global ischaemia followed by 25 min global ischaemia and 30 min reperfusion. Non-preconditioned hearts were subjected to 25 min global ischaemia and 30 min reperfusion. Hearts were freeze-clamped and p38 MAPK activation in tissue lysates was assessed by standard Western blotting techniques, using a dual phospho-p38 MAPK antibody as well as a non-radioactive IP-kinase assay. The results showed that transient dual phosphorylation and activation of p38 MAPK occurs during a 3 × 5 min preconditioning protocol: the activation was maximal during the first episode, becoming progressively lower during the second and third episodes, p38 MAPK activation was significantly less during both sustained ischaemia and reperfusion in preconditioned hearts, when compared with non-preconditioned hearts. Attenuation of p38 MAPK activity during sustained ischaemia and reperfusion was associated with improved functional recovery. The effect of inhibition of p38 MAPK activation on cardioprotection was further evaluated in adult, isolated cardiomyocytes. Administration of SB 203580 (1-10 μM) before and during the preconditioning protocol, had no effect on cell morphology and viability after 2 h hypoxia, compared to untreated preconditioned cardiomyocytes. When administered to non-preconditioned cells before the onset of 2 h hypoxia, it caused a significant improvement in both morphology and viability. In summary, the results suggest that attenuation of the kinase activity during sustained ischaemia and reperfusion may be an essential element of the preconditioning process. © 2001 Academic Press.
dc.description.versionConference Paper
dc.identifier.citationJournal of Molecular and Cellular Cardiology
dc.identifier.citation33
dc.identifier.citation4
dc.identifier.issn222828
dc.identifier.other10.1006/jmcc.2001.1347
dc.identifier.urihttp://hdl.handle.net/10019.1/11328
dc.subjectmitogen activated protein kinase
dc.subjectsynaptophysin
dc.subjectanimal cell
dc.subjectapoptosis
dc.subjectcell death
dc.subjectcell viability
dc.subjectconditioning
dc.subjectconference paper
dc.subjectenzyme activation
dc.subjectenzyme activity
dc.subjectenzyme phosphorylation
dc.subjectheart muscle ischemia
dc.subjectheart muscle perfusion
dc.subjectheart protection
dc.subjecthypoxia
dc.subjectisolated heart
dc.subjectmediator release
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectrat
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectEnzyme Activation
dc.subjectEnzyme Inhibitors
dc.subjectImidazoles
dc.subjectIschemic Preconditioning, Myocardial
dc.subjectMale
dc.subjectMitogen-Activated Protein Kinases
dc.subjectMyocardial Ischemia
dc.subjectMyocardial Reperfusion
dc.subjectMyocardium
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectPyridines
dc.subjectRats
dc.subjectRats, Wistar
dc.titleActivation of p38 MAPK induced by a multi-cycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion
dc.typeConference Paper
Files
Collections
Stellenbosch University - Scopus Publications