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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 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 language	English
Pages (from-to)	1082-1089
Number of pages	8
Journal	Biochemistry (Moscow)
Volume	71
Issue number	10
DOIs	https://doi.org/10.1134/S000629790610004X
Publication status	Published - 2006 Oct

Keywords

Apoptosis
Factor xa
Glutamate toxicity
Hippocampal neurons
Intracellular calcium
Thrombin

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Biochemistry

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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.}",

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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

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Modulation of hippocampal neuron survival by thrombin and factor Xa

Abstract

Keywords

ASJC Scopus subject areas

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