Proteinases of hemostasis are regulators of neurodegenerationстатьяТезисы
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Дата последнего поиска статьи во внешних источниках: 26 января 2018 г.
Аннотация: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.