Modulation of hippocampal neuron survival by thrombin and factor Xa

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

doi:10.1134/S000629790610004X

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)
巻	71
号	10
DOI	https://doi.org/10.1134/S000629790610004X
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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10.1134/S000629790610004X

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title = "Modulation of hippocampal neuron survival by thrombin and factor Xa",

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.",

keywords = "Apoptosis, Factor xa, Glutamate toxicity, Hippocampal neurons, Intracellular calcium, Thrombin",

author = "Gorbacheva, {L. R.} and Storozhevykh, {T. P.} and Pinelis, {V. G.} and S. Ishiwata and Strukova, {S. M.}",

year = "2006",

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AU - Gorbacheva, L. R.

AU - Storozhevykh, T. P.

AU - Pinelis, V. G.

AU - Ishiwata, S.

AU - Strukova, S. M.

PY - 2006/10

Y1 - 2006/10

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Factor xa

KW - Glutamate toxicity

KW - Hippocampal neurons

KW - Intracellular calcium

KW - Thrombin

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Modulation of hippocampal neuron survival by thrombin and factor Xa

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