scholarly journals The roles of factor Va and protein S in formation of the activated protein C/protein S/factor Va inactivation complex

2019 ◽  
Vol 17 (12) ◽  
pp. 2056-2068 ◽  
Author(s):  
Magdalena Gierula ◽  
Isabelle I. Salles‐Crawley ◽  
Salvatore Santamaria ◽  
Adrienn Teraz‐Orosz ◽  
James T. B. Crawley ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
C Protein ◽  
Factor Va ◽  
S Factor

ENDOTHELIUM AND PROTEIN S: SYNTHESIS, RELEASE AND REGULATION OF ANTICOAGULANT ACTIVITY

1987 ◽  
Author(s):  
Peter P Nawroth ◽  
Jerry Brett ◽  
Susan Steinberg ◽  
Charles T Esmon ◽  
David M Stern
Keyword(s):  
Endothelial Cell ◽  
Protein C ◽  
Specific Binding ◽  
Activated Protein C ◽  
Protein S ◽  
Intracellular Protein ◽  
C Protein ◽  
Factor Va ◽  
Intracellular Vesicles ◽  
Anticoagulant Function

The protein C-protein S pathway is closely linked to the vessel wall. In terms of protein C, endothelium has been shown to provide the receptor thrombomodulin, which promotes thrombin-mediated formation of activated protein C. Optimal anticoagulant function of activated protein C requires protein S and a cellular surface. Recent studies have indicated that endothelium can facilitate assembly of the activated protein C-protein S complex and that bovine endothelium expresses specific binding site(s) for protein S which promote its anticoagulant function. Expression of protein S binding sites is subject to down-regulation by Tumor Necrosis Factor (TNF) . Exposure of cultured bovine endothelium to TNF results in decreased 125I-protein s binding and attenuated rates of Factor Va inactivation after 2 hrs followed by negligible 125I-protein S binding and Factor Va inactivation by 10 hrs. These changes persist for over 48 hrs, in contrast to the more transient rise in endothelial cell tissue factor induced by TNF which returns to baseline by 24 hrs.In addition to providing binding sites for protein S, endothelium constitutively synthesizes and releases this vitamin K-dependent anticoagulant cofactor. Release of protein S is blocked by addition of warfarin, indicating that y-carboxylation facilitates the release of intracellular protein S. Morphologic studies, at the level of electron microscope, have shown protein S antigen to be present in cisternae of rough endoplasmic reticulum, the trans face of the golgi and a population of intracellular vesicles which appear to be distributed at the cellular periphery. By immunofluorescence, the distribution of protein S is distinct from that of von Willebrand Factor. The intracellular vesicles containing protein S constitute a storage pool potentially available for rapid release. Treatment of endothelium with norepinephrine results in release of protein S over the next 20 min. Release is half-maximal at a norepinephrine concentration of about 0.1 uM and is not observed with the biologically inactive entantiomer (+) norepinephrine. Norepinephrine-induced release of intracellular protein S can be blocked by prazosine (10-7 7 M), but not by propranolol (10-6 M) or yohimbine (10-5 M). These data are consistent with release of protein S being a receptor-mediated process dependent on an endothelial cell alpha 1 adrenergic receptor. Blockade of norepinephrine-induced release of protein S by pertussis toxin treatment of endothelium further defines the intracellular pathway of protein S and implicates regulatory G proteins in the stimulus-response coupling. Electron microscopic studies have shown that following exposure of endothelium to norepinephrine the intracellular vesicles containing protein S undergo exocytosis at the plasma membrane. These data define a new relationship between the autonomic nervous system and the coagulation mechanism.Protein S is clearly an endothelial cell-associated anticoagulant protein. A specific binding site on the endothelial cell surface can regulate its anticoagulant function on the vessel wall. Endothelial cell synthesis and release of protein S defines a new level of participation of endothelium in the protein C-protein S pathway.

A Novel Functional Assay of Protein C in Human Plasma and fts Comparison with Amidolytic and Anticoagulant Assays

1992 ◽  
Vol 67 (01) ◽  
pp. 046-049 ◽  
Author(s):  
H A Guglielmone ◽  
M A Vides
Keyword(s):  
Oral Anticoagulant ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Normal Subjects ◽  
Test Sample ◽  
Functional Assay ◽  
Fast Method ◽  
Factor Va ◽  
Protein C Activity

SummaryA simple and fast method for the quantitative determination of protein C activity in plasma is here described. The first step consists in the conversion of protein C in the test sample into activated protein C by means of an activator isolated from Southern Copperhead venom. Subsequently, the degradation of factor Va, in presence of protein C-deficient plasma, is measured by the prolongation of the prothrombin time which is proportional to the amount of protein C in the sample. The dose-response curve showed a linear relationship from 6 to 150% protein C activity and the inter- and intra-assay reproducibility was 3.5% and 5.6% respectively. In normal subjects, a mean of protein C level of 98 ± 15% of normal pooled plasma was found. Comparison with the anticoagulant assay in samples of patients with oral anticoagulant, liver cirrhosis, disseminated intravascular coagulation and severe preeclampsia revealed an excellent correlation (r = 0.94, p <0.001). Also, a similar correlation (r = 0.93, p <0.001) existed between amidolytic assay and the method here proposed for all the samples studied without including the oral anticoagulant group. These results allowed us to infer that this method evaluates the ability of protein C to interact with protein S, phospholipids, calcium ions and factor Va.

scholarly journals Binding of protein S to factor Va associated with inhibition of prothrombinase that is independent of activated protein C.

1993 ◽  
Vol 268 (4) ◽  
pp. 2872-2877
Author(s):  
M.J. Heeb ◽  
R.M. Mesters ◽  
G. Tans ◽  
J. Rosing ◽  
J.H. Griffin
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Factor Va

scholarly journals Importance of Protein S and Phospholipid for Activated Protein C-mediated Cleavages in Factor Va

2003 ◽  
Vol 278 (27) ◽  
pp. 24904-24911 ◽  
Author(s):  
Eva A. Norstrøm ◽  
Mårten Steen ◽  
Sinh Tran ◽  
Björn Dahlbäck
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Factor Va

PROTEIN S-C4BP COMPLEX STIMULATES ACTIVATED PROTEIN C-MEDIATED INACTIVATION AT R306 BUT INHIBITS INACTIVATION AT R506 IN FACTOR VA

2007 ◽  
Vol 5 ◽  
pp. P-M-082-P-M-082
Author(s):  
L. Maurissen ◽  
S. Thomassen ◽  
G. Nicolaes ◽  
B. Dahlbäck ◽  
G. Tans ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Factor Va

scholarly journals Increased Thrombophilic Tendency in Pediatric Cystic Fibrosis Patients

2009 ◽  
Vol 16 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Vaughan Williams ◽  
Adrian B. M. Griffiths ◽  
Zen L. Yap ◽  
James Martin ◽  
Gregory Smith ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
General Population ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Activated Protein C Resistance ◽  
Antithrombin Deficiency ◽  
Indwelling Catheters ◽  
C Protein ◽  
Lupus Anticoagulants

Thrombophilia has recently been reported to be increased in patients with cystic fibrosis (CF). We wanted to determine whether this was applicable to our population with CF and how our patients compared to the previously reported groups. Seventy one pediatric CF patients were assessed for a thrombophilic tendency, using a lupus anticoagulant screen, protein C, protein S, antithrombin assay, and activated protein C resistance (APCR) screen. The incidence of activate protein C resistance (4.2%) was within expected limits for the general population as was the incidence of antithrombin deficiency. However there was a marked increase in the incidence of lupus anticoagulants (18%) and 14% and 19.7% of the patients showed a reduced protein C and protein S, respectively, far in excess of the general population. This increased incidence of thrombophilia was not related to any specific CF phenotype and while perturbed liver function cannot be entirely ruled out, it appeared unlikely to be responsible for all the abnormal coagulation findings. Despite the apparent thrombophilic tendency, no clinically evident thrombotic episodes were noted during the study period. Thrombophilia is of concern because of the increasingly frequent placement of indwelling catheters in CF patients. The precise cause for the thrombophilic tendency in CF patients is unknown at this stage.

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