Plasmin on adherent cells: from microvesiculation to apoptosis

Autor: Doeuvre, Loïc, Plawinski, Laurent, Goux, Didier, Vivien, Denis, Anglés-Cano, Eduardo
Přispěvatelé: Angles-Cano, Eduardo, Affording Recovery In Stroke - ARISE - - EC:FP7:HEALTH2008-03-01 - 2013-08-31 - 201024 - VALID, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Inserm, European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement [201024]., European Project: 201024,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ARISE(2008)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Biochemical Journal
Biochemical Journal, 2010, 432 (2), pp.365-73. ⟨10.1042/BJ20100561⟩
ISSN: 0264-6021
1470-8728
DOI: 10.1042/BJ20100561⟩
Popis: International audience; Cell activation by stressors is characterized by a sequence of detectable phenotypic cell changes. A given stimulus, depending on its strength, induces modifications in the activity of membrane phospholipid transporters and calpains, which lead to phosphatidylserine exposure, membrane blebbing and the release of microparticles (nanoscale membrane vesicles). This vesiculation could be considered as a warning signal that may be followed, if the stimulus is maintained, by cell detachment-induced apoptosis. In the present study, plasminogen incubated with adherent cells is converted into plasmin by constitutively expressed tPA (tissue-type plasminogen activator) or uPA (urokinase-type plasminogen activator). Plasmin formed on the cell membrane then induces a unique response characterized by membrane blebbing and vesiculation. Hitherto unknown for plasmin, these membrane changes are similar to those induced by thrombin on platelets. If plasmin formation persists, matrix proteins are then degraded, cells lose their attachments and enter the apoptotic process, characterized by DNA fragmentation and specific ultrastructural features. Since other proteolytic or inflammatory stimuli may evoke similar responses in different types of adherent cells, the proposed experimental procedure can be used to distinguish activated adherent cells from cells entering the apoptotic process. Such a distinction is crucial for evaluating the effects of mediators, inhibitors and potential therapeutic agents.
Databáze: OpenAIRE