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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2010-5-21
pubmed:abstractText
The role of c-Jun NH(2)-terminal kinase 1 (JNK1) in hemostasis and thrombosis remains unclear. We show here, with JNK1-deficient (JNK1(-/-)) mice, that JNK1 plays an important role in platelet biology and thrombus formation. In tail-bleeding assays, JNK1(-/-) mice exhibited longer bleeding times than wild-type mice (396 +/- 39 seconds vs 245 +/- 32 seconds). We also carried out in vitro whole-blood perfusion assays on a collagen matrix under arterial shear conditions. Thrombus formation was significantly reduced for JNK1(-/-) platelets (51%). In an in vivo model of thrombosis induced by photochemical injury to cecum vessels, occlusion times were 4.3 times longer in JNK1(-/-) arterioles than in wild-type arterioles. Moreover, in vitro studies carried out in platelet aggregation conditions demonstrated that, at low doses of agonists, platelet secretion was impaired in JNK1(-/-) platelets, leading to altered integrin alphaIIbbeta3 activation and reduced platelet aggregation, via a mechanism involving protein kinase C. JNK1 thus appears to be essential for platelet secretion in vitro, consistent with its role in thrombus growth in vivo. Finally, we showed that ERK2 and another isoform of JNK affect platelet aggregation through 2 pathways, one dependent and another independent of JNK1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4083-92
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Platelet JNK1 is involved in secretion and thrombus formation.
pubmed:affiliation
Inserm U770, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't