Apoptosis is mediated by cytosolic phospholipase A2 during simulated ischaemia/reperfusion-induced injury in neonatal cardiac myocytes.
It has become increasingly clear that apoptosis plays a major role in ischaemia/reperfusion (I/R)-induced cell death, but the molecular basis of this process remains to be elucidated. Therefore, the aim of this study was to investigate the role of cPLA(2) in MAPK phosphorylation and apoptosis in simulated ischaemia/reperfusion (SI/R)-induced injury in neonatal cardiomyocytes. Inhibition of cPLA(2) with AACOCF(3) significantly improved cell viability during SI/R (60.17+/-1.77 to 80.17+/-1.97%, p<0.05). The increase in cell viability was associated with a significant inhibition of p38 phosphorylation (135.3+/-4.47% to 87.94+/-10.71%, p<0.001) as well as with a significant decrease in caspase-3- (320.32+/-17.32% to 146.7+/-28.69%, p<0.01) and PARP-(263.9+/-8.15% to 154.7+/-2.24%, p<0.001) cleavage during SI/R. This study provides evidence for a role for cPLA(2) during SI/R-induced injury. It appears that p38 MAPK is a central role player in the signalling pathway involved.
Engelbrecht
A-M
AM
Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa. ame@sun.ac.za
Ellis
B
B
D000818:Animals; D017209:Apoptosis; D001095:Arachidonic Acids / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001095:Arachidonic Acids; C081565:arachidonyltrifluoromethane; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D054513:Group IV Phospholipases A2; C505410:Casp3 protein, rat; D053148:Caspase 3