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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Cardiotonic Agents, Enzyme Activation, G(M1) Ganglioside, Ischemic Preconditioning, Myocardial, Lysophospholipids, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Cardiovascular, Myocardial Infarction, Myocardial Reperfusion Injury, Myocardium, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor), Protein Kinase C, Protein Kinase C-epsilon, Protein Transport, Signal Transduction, Sphingosine.
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Does sphingosine kinase activation mediate ischemic preconditioning in murine heart? Context: Phosphorylation of sphingosine by sphingosine kinase (SK) is the rate-limiting step in the cellular synthesis of sphingosine 1-phosphate (S1P). The monoganglioside GM1, which stimulates SK, is cardioprotective in part through increased generation of S1P that protects myocytes by diverse mechanisms. Because protein kinase C (PKC)epsilon activation is necessary for myocardial ischemic preconditioning (IPC) and PKC activators increase SK activity, we tested the hypothesis that SK may be a central mediator of IPC. In adult murine hearts, IPC sufficient to reduce infarct size significantly increased cardiac SK activity, induced translocation of SK protein from the cytosol to membranes, and enhanced cardiac myocyte survival. IPC did not increase SK activity in PKCepsilon-null mice. The SK antagonist N,N-dimethylsphingosine inhibited PKCepsilon activation and directly abolished the protective effects of IPC and the enhanced SK activity induced by IPC.
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These findings demonstrate that PKCepsilon is thus recruited by IPC and induces activation of SK that then mediates IPC-induced cardioprotection in murine heart. Final Decision: yes