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PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation.

Mockridge, JW; Punn, A; Latchman, DS; Marber, MS; Heads, RJ; (2000) PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation. Am J Physiol Heart Circ Physiol , 279 (2) H492-H501. 10.1152/ajpheart.2000.279.2.H492.

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Abstract

In this study we used an in vitro model of delayed preconditioning to investigate activation of mitogen-activated protein kinases (MAPKs) and their potential role in protection. Neonatal rat cardiomyocytes were preconditioned using a buffer containing glycolytic inhibitors and low pH (minimal metabolic preconditioning; MMPC) consisting of modified Krebs buffer, 10 mM 2-deoxyglucose, and 20 mM lactate, pH 6.8, for 2 h followed by 24 h of simulated reperfusion before lethal simulated ischemia (LSI). MAPK activation during the MMPC protocol was determined using phospho-specific antisera and the effect on protection determined following LSI. Rapid, transient phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 MAPK was observed during each of the MMPC, reperfusion, and LSI phases; an effect blocked by MAPK inhibitors PD-98059 and SB-203580, respectively, but not by the protein kinase C (PKC) inhibitor Ro31-8220. However, although MMPC was blocked by Ro31-8220, treatment with the MAPK inhibitors during the preconditioning protocol did not block delayed protection conferred by MMPC. Thus the data suggest that, in this model of delayed preconditioning, protection appears to be PKC dependent but independent of ERK1/2 or p38 MAPK activation.

Type: Article
Title: PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation.
Location: United States
DOI: 10.1152/ajpheart.2000.279.2.H492
Keywords: Animals, Animals, Newborn, Cells, Cultured, Culture Media, Enzyme Inhibitors, Flavonoids, Heart, Hydrogen-Ion Concentration, Imidazoles, Ischemic Preconditioning, Myocardial, Kinetics, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Myocardial Reperfusion, Myocardium, Protein Kinase C, Pyridines, Rats, Rats, Sprague-Dawley, p38 Mitogen-Activated Protein Kinases
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
URI: http://discovery.ucl.ac.uk/id/eprint/25145
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