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The Protective Effect of Activated Protein C as the Baised Agonism in Activation of Protease-activated Receptor 1статья Тезисы
Дата последнего поиска статьи во внешних источниках: 22 февраля 2019 г.
- Авторы: Gorbacheva L., Strukova S.
- Журнал: Research and Practice in Thrombosis and Haemostasis
- Том: 1
- Номер: S1
- Год издания: 2017
- Издательство: John Wiley & Sons
- Местоположение издательства: Hoboken, NJ, United States
- Первая страница: 413
- Последняя страница: 414
- DOI: 10.1002/rth2.12012
- Аннотация: It has been shown recently that the multidirectional effects of thrombin and APC may be due to biased agonism under the action of thrombin and APC proteases on the PAR1 in endothelial cells. Under conditions of biased agonism, APC-specific noncanonic cleavage at Arg46 has been identified in the PAR1 exodomain instead of the canonic cleavage by thrombin at Arg41. We have shown for the first time that a noncanonical PAR1 ligand (NPNDKYEPF amide) protects neurons at glutamate-induced toxicity, mast cells at acute inflammation, astrocytes at ischemia and stimulates the proliferative activity of keratinocytes, like protease APC. These effects of new peptide were abolished by blockage of PAR1. Canonical peptide (TRAP6) has demonstrated proinflammatory and toxic effects on astrocytes, mast cell and neurons, similar to Th. Thus the new peptide-agonist PAR1 simulates APCinduced but not thrombin-induced signaling on different cell types.
- Добавил в систему: Горбачева Любовь Руфэльевна