Document Detail


Role of thiol pathways in TF procoagulant regulation.
MedLine Citation:
PMID:  22401798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The generation of procoagulant Tissue Factor (TF) is crucial for thrombosis. TF contains a surface exposed allosteric disulfide bond that stabilizes the carboxyl-terminal domain involved in ligand interactions with coagulation factors VIIa and X. TF procoagulant activation typically occurs following cellular perturbations that also cause the appearance of procoagulant phosphatidylserine in the outer leaflet of cell membranes. However, thiol modifying agents, without suppressing phosphatidylserine exposure, can prevent TF activation, implicating thiol-disulfide exchange reactions in the regulation of TF procoagulant activity of primary cells. Protein disulfide isomerase (PDI), a regulator of extracellular thiol exchange, is associated with cell surface TF and required for TF-dependent thrombosis in vivo. PDI regulates the thiol-dependent biogenesis of procoagulant microparticles that are released from myeloid cells and smooth muscle cells following activation of the purinergic P2X7 receptor. Genetic deletion of P2X7 signaling attenuates FeCl(3)-induced carotid artery thrombosis in mice, indicating that TF prothrombotic activity is regulated by specific cell signaling pathways in vivo.
Authors:
Wolfram Ruf
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-03-07
Journal Detail:
Title:  Thrombosis research     Volume:  129 Suppl 2     ISSN:  1879-2472     ISO Abbreviation:  Thromb. Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-16     Completed Date:  2012-09-27     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S11-2     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / physiology*
Factor VIIa / metabolism
Factor Xa / metabolism
Humans
Mice
Signal Transduction
Thromboplastin / chemistry,  metabolism*
Thrombosis / metabolism*
Grant Support
ID/Acronym/Agency:
P01 HL031950/HL/NHLBI NIH HHS; P01 HL031950-26A1/HL/NHLBI NIH HHS; P01-HL31950/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9035-58-9/Thromboplastin; EC 3.4.21.21/Factor VIIa; EC 3.4.21.6/Factor Xa
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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