| http://purl.uniprot.org/citations/20348395 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20348395 | http://www.w3.org/2000/01/rdf-schema#comment | "The anticoagulant factor protein S (PS) has direct cellular activities. Lack of PS in mice causes lethal coagulopathy, ischemic/thrombotic injuries, vascular dysgenesis, and blood-brain barrier (BBB) disruption with intracerebral hemorrhages. Thus, we hypothesized that PS maintains and/or enhances the BBB integrity. Using a BBB model with human brain endothelial cells, we show PS inhibits time- and dose-dependently (half maximal effective concentration [EC(50)] = 27 +/-3 nM) oxygen/glucose deprivation-induced BBB breakdown, as demonstrated by measurements of the transmonolayer electrical resistance, permeability of endothelial monolayers to dextran (40 kDa), and rearrangement of F-actin toward the cortical cytoskeletal ring. Using Tyro-3, Axl, and Mer (TAM) receptor, tyrosine kinase silencing through RNA interference, specific N-terminus-blocking antibodies, Tyro3 phosphorylation, and Tyro3-, Axl- and Mer-deficient mouse brain endothelial cells, we show that Tyro3 mediates PS vasculoprotection. After Tyro3 ligation, PS activated sphingosine 1-phosphate receptor (S1P(1)), resulting in Rac1-dependent BBB protection. Using 2-photon in vivo imaging, we show that PS blocks postischemic BBB disruption in Tyro3(+/+), Axl(-/-), and Mer(-/-) mice, but not in Tyro3(-/-) mice or Tyro3(+/+) mice receiving low-dose W146, a S1P(1)-specific antagonist. Our findings indicate that PS protects the BBB integrity via Tyro3 and S1P(1), suggesting potentially novel treatments for neurovascular dysfunction resulting from hypoxic/ischemic BBB damage."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2010-01-262386"xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Zhu D."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Zlokovic B.V."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Singh I."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Zhong Z."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Deane R."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Sagare A."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Bell R.D."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/author | "Winkler E.A."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/pages | "4963-4972"xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/title | "Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor."xsd:string |
| http://purl.uniprot.org/citations/20348395 | http://purl.uniprot.org/core/volume | "115"xsd:string |
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