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• W2080218239 abstract "Neuroprotection against cerebral ischemia conferred by ischemic preconditioning (IPC) requires translocation of epsilon protein kinase C (εPKC). A major goal in our laboratory is to define the cellular targets by which εPKC confers protection. We tested the hypothesis that εPKC targets the mitochondrial K+ATP channel (mtK+ATP) after IPC. Our results demonstrated a rapid translocation of εPKC to rat hippocampal mitochondria after IPC. Because in other tissues εPKC targets mtK+ATP channels, but its presence in brain mitochondria is controversial, we determined the presence of the K+ATP channel-specific subunits (Kir6.1 and Kir6.2) in mitochondria isolated from rat hippocampus. Next, we determined whether mtK+ATP channels play a role in the IPC induction. In hippocampal organotypic slice cultures, IPC and lethal ischemia were induced by oxygen–glucose deprivation. Subsequent cell death in the CA1 region was quantified using propidium iodide staining. Treatment with the K+ATP channel openers diazoxide or pinacidil 48 h prior to lethal ischemia protected hippocampal CA1 neurons, mimicking the induction of neuroprotection conferred by either IPC or εPKC agonist-induced preconditioning. Blockade of mtK+ATP channels using 5-hydroxydecanoic acid abolished the neuroprotection due to either IPC or εPKC preconditioning. Both ischemic and εPKC agonist-mediated preconditioning resulted in phosphorylation of the mtK+ATP channel subunit Kir6.2. After IPC, selective inhibition of εPKC activation prevented Kir6.2 phosphorylation, consistent with Kir6.2 as a phosphorylation target of εPKC or its downstream effectors. Our results support the hypothesis that the brain mtK+ATP channel is an important target of IPC and the signal transduction pathways initiated by εPKC." @default.
• W2080218239 created "2016-06-24" @default.
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• W2080218239 date "2007-12-01" @default.
• W2080218239 modified "2023-10-06" @default.
• W2080218239 title "ɛPKC phosphorylates the mitochondrial K+ATP channel during induction of ischemic preconditioning in the rat hippocampus" @default.
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• W2080218239 doi "https://doi.org/10.1016/j.brainres.2007.09.073" @default.
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