Proteinases of hemostasis are regulators of neurodegenerationстатья Тезисы

Статья опубликована в высокорейтинговом журнале

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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 26 января 2018 г.

Работа с статьей

[1] Gorbacheva L., Abramov E., Strukova S. Proteinases of hemostasis are regulators of neurodegeneration // Journal of Cerebral Blood Flow and Metabolism. — 2017. — Vol. 37, no. 1S. — P. 342–342. Ischemic and hemorrhagic stroke, brain injury accompanied by glutamate (Glu)-induced toxicity, as well as the appearance in the brain tissue of thrombin and activated protein C (APC) as a result of damage to the vessel wall and the blood-brain barrier permeability disorders. The aim of this study was to investigate the effect of thrombin and the APC on the function of cultured neurons and astrocytes of rat brain in toxic conditions. We have shown that thrombin in high (50 nM) concentrations causes the death of more than 30 % of neurons (compared with control), comparable to the Glu-excitotoxicity. Preincubation of cells with APC (1–10 nM) abolished the neuronal death induced by thrombin as well as toxic effects of Glu. Moreover, the thrombin concentration of 1–10 nM prevented apoptosis induced by Glu. Analysis of the proliferation of cultured astrocytes revealed that increasing concentrations of thrombin activates cell proliferation dose-dependent manner. The pretreatment cell cultures with APC blocked this effect of thrombin. It is known that pro-inflammatory effect on endothelial cells is realized through translocation to the nucleus of the transcription factor NF-kB. We have shown that both Glu and thrombin at high toxic concentrations caused translocation of NFkBp65 into the nucleus of neurons. APC protects neurons and reduces the level of NF-kBp65 in the nucleus.We have shown that the action of both thrombin and APC realizes via the receptor-activated proteases 1 (PAR1). Because the effect of these proteases is different, we believe that, despite the involvement of PAR1 in action both proteinases, the result of activation this receptor is probably due to the activation of various intracellular signaling pathways. This can be defined as the activation of different types of G proteins and different directions proteinase activity, splitting different peptide sequences of the receptor. [ DOI ]

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