Effect of enteropeptidase on survival of cultured hippocampal neurons under conditions of glutamate toxicity |
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Authors: | A M Makarova L R Gorbacheva I V Savinkova A G Mikhailova L D Rumsh V G Pinelis S M Strukova |
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Institution: | Faculty of Biology, Lomonosov Moscow State University, Moscow, 119991, Russia. |
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Abstract: | The effects of full-size bovine enteropeptidase (BEK) and of human recombinant light chain enteropeptidase (L-HEP) on survival
of cultured hippocampal neurons were studied under conditions of glutamate excitotoxicity. Low concentrations of L-HEP or
BEK (0.1–1 and 0.1–0.5 nM, respectively) protected hippocampal neurons against the death caused by 100 μM glutamate. Using
the PAR1 (proteinase-activated receptor) antagonist SCH 79797, we revealed a PAR1-dependent mechanism of neuroprotective action
of low concentrations of enteropeptidase. The protective effect of full-size enteropeptidase was not observed at the concentrations
of 1 and 10 nM; moreover, 10 nM of BEK caused death of 88.9% of the neurons, which significantly exceeded the cell death caused
by glutamate (31.9%). Under conditions of glutamate cytotoxicity the survival of neurons was 26.8% higher even in the presence
of 10 nM of L-HEP than in the presence of 10 nM BEK. Pretreatment of cells with 10 nM of either form of enteropeptidase abolished
the protective effect of 10 nM thrombin under glutamate cytotoxicity. High concentrations of BEK and L-HEP caused the death
of neurons mainly through necrosis. |
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