ITEM VIEW

p38 MAPK activation triggers pharmacologically-induced β-adrenergic preconditioning, but not ischaemic preconditioning

dc.contributor.authorMarais E.
dc.contributor.authorGenade S.
dc.contributor.authorStrijdom H.
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.identifier.citationJournal of Molecular and Cellular Cardiology
dc.identifier.citation33
dc.identifier.citation12
dc.identifier.issn222828
dc.identifier.other10.1006/jmcc.2001.1478
dc.identifier.urihttp://hdl.handle.net/10019.1/11327
dc.description.abstractp38 Mitogen-activated protein kinase (p38 MAPK) is activated by short episodes of ischaemia-reperfusion as well as by sustained ischemia followed by reperfusion. Whether activation of this kinase is beneficial or deleterious to the ischaemic heart is still a subject of controversy. Since transient β-adrenergic stimulation (5 min) stimulates p38 MAPK activation and mimics the cardioprotection of ischaemic preconditioning, it was used as a tool to further evaluate the role of this kinase in cardioprotection. The isolated perfused working rat heart, subjected to 25 min ischaemia and 30 min reperfusion was used as experimental model, p38 MAPK and ATF2 activation was determined using Western blots. The results showed that isoproterenol stimulated p38 MAPK in a dose- and time-dependent manner. Ischaemia-induced activation of p38 MAPK could be partially abolished by β- and α1-adrenergic receptor blockade. Isoproterenol activation of the kinase could be abolished by alprenolol and verapamil, but not by 8-cyclopentyladenosine. p38 MAPK activation induced by either a multi-episode preconditioning protocol or isoproterenol (10-7M for 5 min) was associated with a significant reduction in p38 MAPK activation at all time intervals studied during 25 min global ischaemia and at 20 and 30 min of reperfusion, compared with the marked activation observed in untreated non-preconditioned hearts. In each case attenuation of p38 MAPK activation during ischaemia and during reperfusion was associated with improved functional recovery during reperfusion. Cyclic elevations in tissue cAMP during an ischaemic preconditioning protocol acted as trigger of cardioprotection, since pretreatment of such hearts with alprenolol abolished cardioprotection. Mechanical failure in such hearts was characterized by a significant stimulation of p38 MAPK activity during ischaemia and reperfusion. However, p38 MAPK activation during an ischaemic preconditioning protocol did not act as trigger: inhibition of p38 MAPK activation by SB 203580 during the preconditioning phase did not abolish cardioprotection. In fact, functional recovery was significantly better than that of untreated preconditioned hearts. On the other hand, SB 203580, when administered before and during the isoproterenol-preconditioning protocol abolished cardioprotection, suggesting that p38 MAPK activation by a β-adrenergic-induced preconditioning protocol does act as trigger of cardioprotection. In addition, attenuation of p38 MAPK activity during sustained ischaemia and reperfusion as occurs in ischaemic- or isoproterenol-preconditioned hearts, is beneficial. © 2001 Academic Press.
dc.subject4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole
dc.subject8 cyclopentyladenosine verapamil
dc.subjectalprenolol
dc.subjectbeta adrenergic receptor
dc.subjectisoprenaline
dc.subjectmitogen activated protein kinase
dc.subjectunclassified drug
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectdrug effect
dc.subjectenzyme activation
dc.subjectheart infarction prevention
dc.subjectheart muscle ischemia
dc.subjectheart muscle reperfusion
dc.subjectheart protection
dc.subjectmale
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectrat
dc.subjectAdrenergic beta-Agonists
dc.subjectAdrenergic beta-Antagonists
dc.subjectAlprenolol
dc.subjectAnimals
dc.subjectEnzyme Activation
dc.subjectEnzyme Inhibitors
dc.subjectImidazoles
dc.subjectIschemic Preconditioning, Myocardial
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMitogen-Activated Protein Kinases
dc.subjectMyocardial Ischemia
dc.subjectMyocardial Reperfusion
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectPerfusion
dc.subjectPhosphorylation
dc.subjectPyridines
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectReceptors, Adrenergic, beta
dc.titlep38 MAPK activation triggers pharmacologically-induced β-adrenergic preconditioning, but not ischaemic preconditioning
dc.typeArticle
dc.description.versionArticle


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

ITEM VIEW