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MAP-kinase-activated protein kinase 2 expression and activity is induced after neuronal depolarization

Authors

  • Tobias Thomas,

    1. Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
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    • *

      Present address: Department of Neurology, Justus-Liebig-University, Giessen, Germany.

  • Edward Hitti,

    1. Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
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    • Present address: Program in BioMolecular Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

  • Alexey Kotlyarov,

    1. Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
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  • Heidrun Potschka,

    1. Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University, Munich, Germany
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  • Matthias Gaestel

    1. Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
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Dr M. Gaestel, as above.
E-mail: gaestel.matthias@mh-hannover.de

Abstract

Mitogen-activated protein kinase-activated protein kinase (MK)2 is one of several downstream targets of p38 mitogen-activated protein kinase and has a well documented role in inflammation. Here, we describe a possible new function of MK2. We show that triggering depolarization by potassium chloride or increasing the cellular cAMP by forskolin treatment led to elevated levels of expression and activity of mouse MK2. In both treatments, the kinase inhibitor H89 completely prevented the up-regulation of MK2 at the transcript level. By the use of different cell lines we demonstrated that the induction of MK2 expression is characteristic of neuronal cells and is absent in fibroblasts, macrophages and kidney cells. In vivo, induction of a status epilepticus by systemic administration of the chemoconvulsant kainic acid resulted in markedly reduced neurodegeneration in the pyramidal layer of the hippocampus, dentate gyrus and hilus of MK2-deficient mice compared with wild-type mice. Together, our data suggest a possible role of MK2 in the cellular response after neuronal depolarization, in particular in excitotoxicity.

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