Abstract Number: PB2033
Meeting: ISTH 2020 Congress
Background: Mast cells (MC), neurons and astrocytes are the main participants in neuroinflammation, which is a characteristic feature of neurodegenerative disorders. The activation of PAR1 is the key point in the coupling of coagulation and neuroinflammation processes in the brain.
Aims: To investigate the participation of PAR1-agonists – thrombin, APC and its functional analogue, the new peptide 9 (AP9), an analogue of the “tethered ligand” released from PAR1 by APC – in the model of the neuroinflammation in vitro.
Methods: To create the model of neuroinflammation in vitro, MC, astrocytes and neurons were used. The toxic effect of activated MC on neurons or astrocytes and effects of proinflammatory factors on cells were estimated by using a morphological and biochemical analysis of survival. The intracellular calcium was measured by FURA-2AM. The change in the cytoskeleton was carried out by immunocytochemical staining.
Results: AP9 by PAR1 prevented the neuronal death at excitotoxicity, similar to APC. APC and AP9 did not change the [Ca2+]i in neurons, but AP9, not APC, decreased Ca-influx in MC. APC and AP9 significantly increased the percentage of neurons that restored the basal level of calcium after the excitotoxicity. Activation of cells by thrombin(50 nM), like as proinflammatory factors, leads to disorganization and re-distribution of the actin cytoskeleton, however, preincubation of MC with the AP9 and APC promotes actin ordering, stabilize cell membranes and reducing secretion similar to control. Pre-treatment of MC with the AP9 significantly reduced the level of IL-6 secretion by cells during co-cultivation of astrocytes and MC. Also, AP9 by PAR1 leads to decrease toxic effect of MC on neurons and a decrease in the proportion of apoptotic cells, like APC.
Conclusions: PAR1-agonists-AP9 and APC exert an anti-inflammatory and protective actions, in the model of neuroinflammation in vitro.
This study was supported by RFBR 19-015-00529.
To cite this abstract in AMA style:Babkina I, Gorbacheva L. The Protective Effects of PAR1-agonists – Thrombin, Activated Protein C and Peptide 9 in the Model of the Neuroinflammation in vitro [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-protective-effects-of-par1-agonists-thrombin-activated-protein-c-and-peptide-9-in-the-model-of-the-neuroinflammation-in-vitro/. Accessed January 26, 2022.
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