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Activated protein C is the regulator of the NF-κB activity under the conditions of glutamate toxicity

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Activated protein C (APC) is one of the key proteinases of hemostasis exhibiting anti-coagulant, anti-inflammatory, and protective functions. In the present work, the anti-apoptotic effect of the proteinase on the glutamate toxicity model in cultured hippocampal neurons has been discovered. It is demonstrated that high concentrations of glutamate induce translocation of p65 subunit of transcription factor NF-κB into the nucleus, while low concentrations of APC prevent this effect of the neurotransmitter. Moreover, helenalin, a specific inhibitor of NF-κBp65, similar to APC, increased survival of neurons under toxic conditions. Using specific blocking antibodies, we have revealed that APC via its own receptor (endothelial protein C receptor) and protease activated receptor 1 (PAR1) inhibits glutamate-induced activation of transcription factor NF-κB. Thus, APC in low concentrations protects hippocampal neurons from glutamate-induced death through a receptor-dependent regulation of the activity of p65 subunit of transcription factor NF-κB.

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Authors and Affiliations

  1. Biological Faculty, Moscow Lomonosov State University, Moscow, 119991, Russia

    L. R. Gorbacheva & S. M. Strukova

  2. Ivanovo State University, Ivanovo, Russia

    L. R. Gorbacheva

  3. Centre for Children’s Health, Russian Academy of Medical Sciences, Moscow, Russia

    V. G. Pinelis

  4. Institute for Neurobiochemistry, Otto-von-Guericke University, Magdeburg, Germany

    G. Reiser

Authors
  1. L. R. Gorbacheva
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  2. V. G. Pinelis
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  3. G. Reiser
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  4. S. M. Strukova
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Correspondence to L. R. Gorbacheva.

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Original Russian Text © L.R. Gorbacheva, V.G. Pinelis, G. Reiser, S.M. Strukova, 2011, published in Biologicheskie Membrany, 2011, Vol. 28, No. 6, pp. 495–506.

The article was translated by the authors.

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Gorbacheva, L.R., Pinelis, V.G., Reiser, G. et al. Activated protein C is the regulator of the NF-κB activity under the conditions of glutamate toxicity. Biochem. Moscow Suppl. Ser. A 6, 56–66 (2012). https://doi.org/10.1134/S1990747811060067

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  • DOI: https://doi.org/10.1134/S1990747811060067

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