Endothelial protein C receptor is expressed in rat cortical and hippocampal neurons and is necessary for protective effect of activated protein C at glutamate excitotoxicity

Lyubov Gorbacheva, Olga Davidova, Elena Sokolova, Shin'Ichi Ishiwata, Vsevolod Pinelis, Svetlana Strukova, Georg Reiser

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Activated protein C (APC) is an anticoagulant and anti-inflammatory factor that acts via endothelial protein C receptor (EPCR). Interestingly, APC also exhibits neuroprotective activities. In the present study, we demonstrate for the first time expression of EPCR, the receptor for APC, in rat cortical and hippocampal neurons. Moreover, exposing the neurons to glutamate excitotoxicity we studied the functional consequence of the expression of EPCR. By cytotoxicity assay we showed that EPCR was necessary for the APC-mediated protective effect in both neuronal cell types in culture. The effect of APC was abrogated in the presence of blocking EPCR antibodies. Analysis of neuronal death by cell labelling with dyes which allow distinguishing living and dead cells confirmed that the anti-apoptotic effect of APC was dependent on both EPCR and protease-activated receptor-1. Thus, we suggest that binding of APC to EPCR on neurons and subsequent activation of protease-activated receptor-1 by the complex of APC-EPCR promotes survival mechanisms after exposure of neurons to damaging factors.

    Original languageEnglish
    Pages (from-to)967-975
    Number of pages9
    JournalJournal of Neurochemistry
    Volume111
    Issue number4
    DOIs
    Publication statusPublished - 2009 Nov

    Keywords

    • Activated protein C
    • Coagulation proteases
    • Excitotoxicity
    • Neuroprotection
    • Thrombin

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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