Ischaemic preconditioning and TNF-α-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 A(2) (cPLA(2)) 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-a and cPLA(2) activities during cytoprotection is poorly understood. Therefore, we examined the role of cPLA(2) in TNF-alpha-mediated (TNF-PC) and ischaemic preconditioning (IPC) in tolerance to ischaemia (SI) in C2C12 myotubes. Significant decreases in cPLA(2) 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-cPLA(2) to the nuclear region in SI compared to TNF-PC and IPC. These data suggest a p38 driven cPLA(2) translocation pattern, with a possible role for cPLA(2) in deciding cell fate. (C) 2008 Elsevier Ltd. All rights reserved.