Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4342148 | Neuroscience | 2007 | 11 Pages |
Abstract
The signaling pathway of cyclooxygenase-2 (COX-2) induction following ischemic preconditioning (IPC) in brain remains undefined. To determine role of COX-2 in ischemic preconditioning, we used two in vitro models: mixed cortical neuron/astrocyte cell cultures and organotypic hippocampal slice cultures. We simulated IPC by exposing cell or slice cultures to 1 h or 15 min of oxygen/glucose deprivation (OGD), respectively, 48 h prior to ischemia. To mimic ischemia in vitro, we exposed cell or slice cultures to OGD of 4 h or 40 min, respectively. In cell cultures, these experiments revealed that COX-2 induction peaked at 24 h following IPC in cell culture. Inhibition of COX-2 activation with 50 μM NS-398 (a COX-2 selective inhibitor) abolished IPC-mediated neuroprotection in both in vitro models. Next, we tested whether ε protein kinase C (εPKC) and extracellular signal regulated kinase 1/2 (ERK1/2) activation was involved in IPC-mediated neuroprotection and COX-2 expression in cell culture. Cell cultures were treated with an εPKC-specific activating peptide (ÏεRACK, 100 nM) for 1 h, and 48 h later were exposed to OGD. εPKC activation increased ERK1/2 phosphorylation and COX-2 induction and conferred neuroprotection similar to IPC. Additionally, inhibition of either εPKC or ERK1/2 activation abolished COX-2 expression and neuroprotection due to ischemic preconditioning. These results demonstrate a crucial role for the εPKCâERK1/2âCOX-2 pathway in the induction of neuroprotection via ischemic preconditioning.
Keywords
PBS-THBSSNF-κBNeuNPD98059PGE2OGDextracellular signal regulated kinase 1/2GFAPCCDEP2IPCFBSCOXNS-398BSAERK1/2MAPKischemic preconditioningbovine serum albumincyclooxygenaseoxygen/glucose deprivationIschemiaminimum essential mediumLSMfetal bovine serumNuclear factor-kappa Borganotypic hippocampal slice cultureslactate dehydrogenaseLDHMEMNeuroprotectionHanks’ balanced salt solutionLaser scanning microscopyGlial fibrillary acidic proteinmitogen-activated protein kinasePropidium iodideProstaglandin E2prostaglandinCell culturesProstaglandin E2 receptor
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Authors
E. Kim, A.P. Raval, R.A. DeFazio, M.A. Perez-Pinzon,