Ischaemic preconditioning and TNF-alpha-mediated preconditioning is associated with a differential cPLA2 translocation pattern in early ischaemia.
Both the cytokine tumour necrosis factor-alpha (TNF-alpha) and the enzyme cytosolic phospholipase A2 (cPLA2) have been implicated in ischaemic injury. Apart from the induction of apoptosis, TNF-alpha also mediates cytoprotection when present in low concentrations. However, the relationship between TNF-alpha and cPLA2 activities during cytoprotection is poorly understood. Therefore, we examined the role of cPLA2 in TNF-alpha-mediated (TNF-PC) and ischaemic preconditioning (IPC) in tolerance to ischaemia (SI) in C2C12 myotubes. Significant decreases in cPLA2 phosphorylation in SI compared with the preconditioned groups were observed. This was also mirrored by the p38 mitogen activated protein kinase (MAPK) phosphorylation pattern. These results correlated with fluorescence- and three-dimensional imaging, demonstrating increased translocation of phospho-cPLA2 to the nuclear region in SI compared to TNF-PC and IPC. These data suggest a p38 driven cPLA2 translocation pattern, with a possible role for cPLA2 in deciding cell fate.
Loos
B
B
Department of Physiological Sciences, University of Stellenbosch, Meriman Street, Stellenbosch 7600, Republic of South Africa.
Smith
R
R
Engelbrecht
A-M
AM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins; D010766:Phosphorylation / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; D014409:Tumor Necrosis Factor-alpha; C049312:nuclear pore protein p62; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D054513:Group IV Phospholipases A2; C505409:Casp3 protein, mouse; D053148:Caspase 3