Modulation of hippocampal neuron survival by thrombin and factor Xa

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

*この研究の対応する著者

    研究成果: Article査読

    22 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ページ(範囲)1082-1089
    ページ数8
    ジャーナルBiochemistry (Moscow)
    71
    10
    DOI
    出版ステータスPublished - 2006 10月

    ASJC Scopus subject areas

    • 生化学、遺伝学、分子生物学(全般)
    • 生化学

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