Abstract:
:In order to explore the mechanisms leading to conformational changes of the vitronectin receptor alphavbeta3 following ligand or divalent cation binding, we have investigated the expression of epitopes known as ligand-induced binding sites (LIBS) on beta3 cytoplasmic tail mutants expressed in CHO cells. Truncation of the entire beta3 cytoplasmic domain induced constitutive LIBS exposure on alphavbeta3 and alphaIIbeta3. Deletion of the C-terminal NITY759 sequence or disruption of the NPLY747 motif by a Y747A substitution impaired extracellular conformational changes on alphavbeta3 following RGDS, echistatin or Mn2+ binding, whereas the substitutions Y747F, Y759A or Y759F allowed normal LIBS exposure. Furthermore, metabolic energy depletion totally prevented Mn2+-dependent LIBS exposure, but had only a minor effect on RGDS-induced conformational changes. Our results demonstrate that the structural integrity of the NPLY747 motif in the beta3 cytoplasmic domain, rather than potential phosphorylation of Tyr747 or Tyr759, is a prerequisite for conformational changes within the alphavbeta3 ectodomain, and suggest that two different mechanisms are responsible for RGDS- and Mn2+-dependent conformational changes.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Schaffner-Reckinger E,Brons NH,Kieffer Nkeywords:
subject
Has Abstractpub_date
2001-04-01 00:00:00pages
716-23issue
4eissn
0340-6245issn
2567-689Xpii
01040716journal_volume
85pub_type
杂志文章abstract::Pannexin1 (Panx1) forms ATP channels that play a critical role in the immune response by reinforcing purinergic signal amplification in the immune synapse. Platelets express Panx1 and given the importance of ATP release in platelets, we investigated Panx1 function in platelet aggregation and the potential impact of ge...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-11-0981
更新日期:2015-08-01 00:00:00
abstract::The biologically active components from Viperidae venoms specifically affect cell-matrix interactions, and have been utilized for developing anti-adhesive therapy as anti-thrombotic and anti-angiogenic agents. Utilizing platelet aggregometry coupled with flow cytometry, we found that a metalloproteinase isolated from ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-07-0426
更新日期:2004-02-01 00:00:00
abstract::Two polymorphisms in the endothelial protein C receptor (EPCR) gene, 4600A/G and 4678G/C, have been reported to influence the risk of venous thromboembolism (VTE). The objective of this study was to assess whether these polymorphisms modify the risk of VTE in carriers of factor V (FV) Leiden. We genotyped 295 carriers...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-02-0089
更新日期:2005-08-01 00:00:00
abstract::There are conflicting views on the effects of age, gene source and familial severity on levels of factor VIII in carriers of haemophilia. Different workers have found that factor VIII increases with age, is higher in paternal carriers, and is higher in carriers from families with more severe haemophilia. Other workers...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-10-31 00:00:00
abstract::Recurrent joint bleeding is the most common manifestation of haemophilia resulting in haemophilic arthropathy (HA). The exact pathophysiology is unknown, but it is suggested that arthropathy is stimulated by liberation of fibrinolytic activators from the synovium during haemarthrosis. The aim of this study was to test...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-01-0080
更新日期:2013-07-01 00:00:00
abstract::Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved in host defence du...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-12-0920
更新日期:2017-07-26 00:00:00
abstract::Edoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke prevention in patients with atrial fibrillation and for the treatment and secondary prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism. Among elderly patients who require anticoagulation the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH14-06-0547
更新日期:2015-04-01 00:00:00
abstract::Alpha 2-macroglobulin (alpha 2 M) in vitro inhibits numerous proteinases that are generated during inflammatory reactions and therefore, probably plays an important role in diseases such as sepsis. To monitor the state of alpha 2 M in sepsis, we developed novel assays for functional and inactive alpha 2M. Functional a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-01-23 00:00:00
abstract::The characterization of mutations in von Willebrand disease provides useful insight into the synthesis, structure, and function of von Willebrand factor. This growing body of information has prompted a reclassification of vWD types that is intended to reflect distinct pathophysiologic mechanisms. Despite this apparent...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1995-07-01 00:00:00
abstract::Reactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand's disease (vWd). One quinine-dependent antibody (Q.Ab) caused platelet aggregation and [14C] serotonin release with only 7 of 12 normal donors,...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-02-28 00:00:00
abstract::Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified alpha 2-antiplasmin depleted plasma (alpha 2-antiplasmin concentration less than 2%). ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-12-27 00:00:00
abstract::Angiogenic activity and formation of a vascular network facilitate tumor perfusion and play a critical role in tumor growth and metastasis. Tumor vasculature may be visualized by means of parametric imaging of specific morphological and physiological characteristics that collectively describe its properties. In this r...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The -323A2 allele in the promoter is known to be associated with low FVII leve...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0130
更新日期:2004-09-01 00:00:00
abstract::According to some authors factor VIII procoagulant activity may be dissociable from carrier protein (MW approximately 2 X 10(6) by agarose gel filtration, e.g. at high ionic strength. We were able to reproduce this phenomenon. However, addition of protease inhibitor (Trasylol) prevented the appearance of low molecular...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-02-29 00:00:00
abstract::The administration of recombinant activated factor VII (rFVIIa) by continuous infusion has provided a safe and convenient alternative to bolus injections in haemophiliacs with inhibitors, but it has only been reported in a single case with congenital factor VII (FVII) deficiency. The results of 12 consecutive surgical...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1160/TH05-05-0342
更新日期:2005-12-01 00:00:00
abstract::Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1 (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation of oxidative stress and/or NO bioavailability. We aimed to assess whether endurance exercise which is known to be cardioprotective could beneficially affect thes...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-03-0158
更新日期:2005-12-01 00:00:00
abstract::The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-11-0873
更新日期:2017-05-03 00:00:00
abstract::Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical development. The primary objective of the present study was to assess the pharmacodynamics (PD) and safety of enoxaparin 1 mg/kg followed 12 hours (h) post-dose by edoxaban 60 mg, which is the regimen being used in the phase III study of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH11-09-0676
更新日期:2012-07-01 00:00:00
abstract::In The Netherlands, a particular coagulometer method for prothrombin time (PT) determination with reduced sample and reagent volumes is used by 62% of the laboratories controlling oral anticoagulant therapy. This "micro-method" has been calibrated against the manual tilt-tube technique for PT determination by six Dutc...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1989-04-25 00:00:00
abstract::We have investigated the intracellular mechanisms involved in microtubular remodelling by thrombin and its possible involvement in platelet aggregation and secretion. Platelet stimulation with thrombin induces a time- and concentration-dependent regulation of the microtubular content, which was found to be maximally e...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-08-01 00:00:00
abstract::ADP or thrombin caused a transient change in creatine phosphate (CP) content of rat platelets. At 25 degrees C the CP content decreased most 30 sec after the addition of ADP or thrombin and recovered thereafter. ATP or AMP was without effect. The rat platelets aggregated at 25 degrees C by ADP or thrombin, but the cha...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-08-31 00:00:00
abstract::An assay of human antiplasmins has been developed utilizing radial diffusion of plasma from wells cut in plasmin-enriched, fibrinogen-agarose plates. After diffusion the fibrinogen is clotted. Zones of fibrin protected from background fibrinolysis develop as the result of plasma antiplasmin activity. A pooled plasma s...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-04-30 00:00:00
abstract::Human tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-04-01 00:00:00
abstract::Vascular smooth muscle cell (VSMC) proliferation occurs in vascular obstructive events such as atherosclerosis and restenosis. We previously showed that Notch receptors are induced in smooth muscle cells during vascular remodeling. Our goal was to determine the mechanisms employed by Notch signaling to regulate prolif...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-04-0224
更新日期:2006-09-01 00:00:00
abstract::Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numb...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-06-0433
更新日期:2017-12-01 00:00:00
abstract::Thrombospondin, a trimeric glycoprotein contained in the platelet alpha-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-04-08 00:00:00
abstract::Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-04-01 00:00:00
abstract::Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L), chem...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-12-0774
更新日期:2005-06-01 00:00:00
abstract::The turnover of recombinant pro-urokinase (Rec-pro-UK), recombinant urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) was studied in rabbits and in squirrel monkeys (Saimiri sciureus). Following intravenous injection, urokinase activity disappeared rapidly from the blood. The initial disappearance rate could b...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-08-31 00:00:00
abstract::The ADP-induced release of 3H-serotonin from human platelets in heparinized platelets rich plasma is markedly stimulated by the addition of sodium citrate. The aggregation and release that is induced by collagen is less affected by citrate. Data is presented that supports the view that the effects of citrate on both A...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-08-31 00:00:00