Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity

L. R. Gorbacheva, T. P. Storozhevykh, V. G. Pinelis, O. N. Davydova, S. Ishiwata, S. M. Strukova

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    The effect of an anticoagulant and cytoprotector blood serine proteinase-activated protein C (APC)-on survival of cultured hippocampal and cortical neurons under conditions of glutamate-induced excitotoxicity has been studied. Low concentrations of APC (0.01-10 nM) did not cause neuron death, but in the narrow range of low concentrations APC twofold and stronger decreased cell death caused by glutamate toxicity. High concentrations of APC (> 50 nM) induced the death of hippocampal neurons similarly to the toxic action of glutamate. The neuroprotective effect of APC on the neurons was mediated by type 1 proteinase-activated receptor (PAR1), because the inactivation of the enzyme with phenylmethylsulfonyl fluoride or PAR1 blockade by a PAR1 peptide antagonist ((Tyr1)-TRAP-7) prevented the protective effect of APC. Moreover, APC inhibited the proapoptotic effect of 10 nM thrombin on the neurons. Geldanamycin, a specific inhibitor of heat shock protein Hsp90, completely abolished the antiapoptotic effect of 0.1 nM APC on glutamate-induced cytotoxicity in the hippocampal neurons. Thus, APC at low concentrations, activating PAR1, prevents the death of hippocampal and cortical neurons under conditions of glutamate excitotoxicity.

    Original languageEnglish
    Pages (from-to)717-724
    Number of pages8
    JournalBiochemistry (Moscow)
    Volume73
    Issue number6
    DOIs
    Publication statusPublished - 2008 Jun

    Fingerprint

    PAR-1 Receptor
    Protein C
    Neurons
    Glutamic Acid
    Phenylmethylsulfonyl Fluoride
    Toxic Actions
    Serine Proteases
    Neuroprotective Agents
    Cell death
    Cytotoxicity
    Heat-Shock Proteins
    Thrombin
    Anticoagulants
    Toxicity
    Cause of Death
    Blood
    Cell Death

    Keywords

    • Activated protein C
    • Apoptosis
    • Geldanamycin
    • Glutamate toxicity
    • Hippocampal and cortical neurons
    • Proteinase-activated receptor

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Biochemistry

    Cite this

    Gorbacheva, L. R., Storozhevykh, T. P., Pinelis, V. G., Davydova, O. N., Ishiwata, S., & Strukova, S. M. (2008). Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity. Biochemistry (Moscow), 73(6), 717-724. https://doi.org/10.1134/S0006297908060138

    Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity. / Gorbacheva, L. R.; Storozhevykh, T. P.; Pinelis, V. G.; Davydova, O. N.; Ishiwata, S.; Strukova, S. M.

    In: Biochemistry (Moscow), Vol. 73, No. 6, 06.2008, p. 717-724.

    Research output: Contribution to journalArticle

    Gorbacheva, LR, Storozhevykh, TP, Pinelis, VG, Davydova, ON, Ishiwata, S & Strukova, SM 2008, 'Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity', Biochemistry (Moscow), vol. 73, no. 6, pp. 717-724. https://doi.org/10.1134/S0006297908060138
    Gorbacheva, L. R. ; Storozhevykh, T. P. ; Pinelis, V. G. ; Davydova, O. N. ; Ishiwata, S. ; Strukova, S. M. / Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity. In: Biochemistry (Moscow). 2008 ; Vol. 73, No. 6. pp. 717-724.
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