Modulation of hippocampal neuron survival by thrombin and factor Xa

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

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Effects of thrombin, factor Xa (FXa), and protease-activated receptor 1 and 2 agonist peptides (PAR1-AP and PAR2-AP) on survival and intracellular Ca 2+ homeostasis in hippocampal neuron cultures treated with cytotoxic doses of glutamate were investigated. It is shown that at low concentrations (≤10 nM) thrombin and FXa protect neurons from glutamate-induced excitotoxicity. Inactivation of the proteases blocked the neuroprotective effect. Using PAR1-AP, PAR2-AP, and PAR1 antagonist, we have demonstrated that the neuroprotective effect of thrombin is mediated through activation of PAR1, whereas the effect of FXa may involve novel subtype(s) of PARs. Unlike FXa, thrombin induced transient intracellular calcium signal in hippocampal neurons, which was mainly mediated via IP3 receptors of the endoplasmic reticulum. Both of the serine proteases improved the recovery of neuronal Ca2+ homeostasis after glutamate treatment.

    Original languageEnglish
    Pages (from-to)1082-1089
    Number of pages8
    JournalBiochemistry (Moscow)
    Volume71
    Issue number10
    DOIs
    Publication statusPublished - 2006 Oct

    Keywords

    • Apoptosis
    • Factor xa
    • Glutamate toxicity
    • Hippocampal neurons
    • Intracellular calcium
    • Thrombin

    ASJC Scopus subject areas

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

    Fingerprint Dive into the research topics of 'Modulation of hippocampal neuron survival by thrombin and factor Xa'. Together they form a unique fingerprint.

  • Cite this

    Gorbacheva, L. R., Storozhevykh, T. P., Pinelis, V. G., Ishiwata, S., & Strukova, S. M. (2006). Modulation of hippocampal neuron survival by thrombin and factor Xa. Biochemistry (Moscow), 71(10), 1082-1089. https://doi.org/10.1134/S000629790610004X