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dc.contributor.author
Devanathan, Vasudharani
dc.contributor.author
Hagedorn, Ina
dc.contributor.author
Köhler, David
dc.contributor.author
Pexa, Katja
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Cherpokova, Deya
dc.contributor.author
Kraft, Peter
dc.contributor.author
Singh, Madhurendra
dc.contributor.author
Rosenberger, Peter
dc.contributor.author
Stoll, Guido
dc.contributor.author
Birnbaumer, Lutz
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Piekorz, Roland P.
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Beer-Hammer, Sandra
dc.contributor.author
Nieswandt, Bernhard
dc.contributor.author
Nürnberg, Bernd
dc.date.available
2018-04-26T14:32:56Z
dc.date.issued
2015-05
dc.identifier.citation
Devanathan, Vasudharani; Hagedorn, Ina; Köhler, David; Pexa, Katja; Cherpokova, Deya; et al.; Platelet G i protein Gα i2 is an essential mediator of thrombo-inflammatory organ damage in mice; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 20; 5-2015; 6491-6496
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/43529
dc.description.abstract
Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury following ischemia and reperfusion. Important regulators of platelet function are G proteins controlled by seven transmembrane receptors. The Gi protein Gα(i2) mediates platelet activation in vitro, but its in vivo role in hemostasis, arterial thrombosis, and postischemic infarct progression remains to be determined. Here we show that mice lacking Gα(i2) exhibit prolonged tail-bleeding times and markedly impaired thrombus formation and stability in different models of arterial thrombosis. We thus generated mice selectively lacking Gα(i2) in megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to those in global Gα(i2)-deficient mice. To examine the impact of platelet Gα(i2) in postischemic thrombo-inflammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to experimental models of cerebral and myocardial ischemia/reperfusion injury. In the model of transient middle cerebral artery occlusion stroke Gna(i2)(fl/fl)/PF4-Cre mice developed significantly smaller brain infarcts and fewer neurological deficits than littermate controls. Following myocardial ischemia, Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which correlated with diminished formation of the ADP-dependent platelet neutrophil complex. In conclusion, our data provide definitive evidence that platelet Gα(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
G Proteins
dc.subject
Platelets
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Ischemia Reperfusion Injury
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P2y12 Receptor
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Thrombosis
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Platelet G i protein Gα i2 is an essential mediator of thrombo-inflammatory organ damage in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-09T14:47:02Z
dc.journal.volume
112
dc.journal.number
20
dc.journal.pagination
6491-6496
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Devanathan, Vasudharani. University of Tübingen; Alemania
dc.description.fil
Fil: Hagedorn, Ina. University Hospital; Alemania
dc.description.fil
Fil: Köhler, David. University of Tübingen; Alemania
dc.description.fil
Fil: Pexa, Katja. Universitat Dusseldorf; Alemania
dc.description.fil
Fil: Cherpokova, Deya. University Hospital; Alemania
dc.description.fil
Fil: Kraft, Peter. Universität Würzburg; Alemania
dc.description.fil
Fil: Singh, Madhurendra. Universitat Dusseldorf; Alemania
dc.description.fil
Fil: Rosenberger, Peter. University of Tübingen; Alemania
dc.description.fil
Fil: Stoll, Guido. Universität Würzburg; Alemania
dc.description.fil
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Research Triangle Park; Alemania
dc.description.fil
Fil: Piekorz, Roland P.. Universitat Dusseldorf; Alemania
dc.description.fil
Fil: Beer-Hammer, Sandra. University of Tübingen; Alemania
dc.description.fil
Fil: Nieswandt, Bernhard. University Hospital; Alemania
dc.description.fil
Fil: Nürnberg, Bernd. University of Tübingen; Alemania
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1505887112
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/20/6491


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