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Tytuł pozycji:

Caveolae optimize tissue factor-Factor VIIa inhibitory activity of cell-surface-associated tissue factor pathway inhibitor.

Tytuł :
Caveolae optimize tissue factor-Factor VIIa inhibitory activity of cell-surface-associated tissue factor pathway inhibitor.
Autorzy :
Maroney SA; Blood Research Institute, Blood Center of Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53201, USA.
Ellery PE
Wood JP
Ferrel JP
Bonesho CE
Mast AE
Pokaż więcej
Źródło :
The Biochemical journal [Biochem J] 2012 Apr 01; Vol. 443 (1), pp. 259-66.
Typ publikacji :
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
MeSH Terms :
Caveolae/*metabolism
Factor VIIa/*metabolism
GPI-Linked Proteins/*metabolism
Lipoproteins/*metabolism
Animals ; Blood Coagulation ; Blood Coagulation Tests ; CHO Cells ; Cell Membrane/metabolism ; Cholesterol/deficiency ; Cholesterol/metabolism ; Cricetinae ; Factor VIIa/antagonists & inhibitors ; Factor Xa/metabolism ; Factor Xa Inhibitors ; Human Umbilical Vein Endothelial Cells ; Humans ; Protein Transport ; Recombinant Fusion Proteins/metabolism ; beta-Cyclodextrins
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Grant Information :
K01 HL096419 United States HL NHLBI NIH HHS; HL007209 United States HL NHLBI NIH HHS; T32 HL007209 United States HL NHLBI NIH HHS; UL1 TR000055 United States TR NCATS NIH HHS; HL068835 United States HL NHLBI NIH HHS; HL091469 United States HL NHLBI NIH HHS; R01 HL091469 United States HL NHLBI NIH HHS; R01 HL149364 United States HL NHLBI NIH HHS; R01 HL068835 United States HL NHLBI NIH HHS
Substance Nomenclature :
0 (Factor Xa Inhibitors)
0 (GPI-Linked Proteins)
0 (Lipoproteins)
0 (Recombinant Fusion Proteins)
0 (beta-Cyclodextrins)
0 (lipoprotein-associated coagulation inhibitor)
0 (methyl-beta-cyclodextrin)
97C5T2UQ7J (Cholesterol)
EC 3.4.21.21 (Factor VIIa)
EC 3.4.21.6 (Factor Xa)
Entry Date(s) :
Date Created: 20120114 Date Completed: 20120521 Latest Revision: 20211021
Update Code :
20211105
PubMed Central ID :
PMC3549619
DOI :
10.1042/BJ20111994
PMID :
22239091
Czasopismo naukowe
TFPI (tissue factor pathway inhibitor) is an anticoagulant protein that prevents intravascular coagulation through inhibition of fXa (Factor Xa) and the TF (tissue factor)-fVIIa (Factor VIIa) complex. Localization of TFPI within caveolae enhances its anticoagulant activity. To define further how caveolae contribute to TFPI anticoagulant activity, CHO (Chinese-hamster ovary) cells were co-transfected with TF and membrane-associated TFPI targeted to either caveolae [TFPI-GPI (TFPI-glycosylphosphatidylinositol anchor chimaera)] or to bulk plasma membrane [TFPI-TM (TFPI-transmembrane anchor chimaera)]. Stable clones had equal expression of surface TF and TFPI. TX-114 cellular lysis confirmed localization of TFPI-GPI to detergent-insoluble membrane fractions, whereas TFPI-TM localized to the aqueous phase. TFPI-GPI and TFPI-TM were equally effective direct inhibitors of fXa in amidolytic assays. However, TFPI-GPI was a significantly better inhibitor of TF-fVIIa than TFPI-TM, as measured in both amidolytic and plasma-clotting assays. Disrupting caveolae by removing membrane cholesterol from EA.hy926 cells, which make TFPIα, CHO cells transfected with TFPIβ and HUVECs (human umbilical vein endothelial cells) did not affect their fXa inhibition, but significantly decreased their inhibition of TF-fVIIa. These studies confirm and quantify the enhanced anticoagulant activity of TFPI localized within caveolae, demonstrate that caveolae enhance the inhibitory activity of both TFPI isoforms and define the effect of caveolae as specifically enhancing the anti-TF activity of TFPI.

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