Anticoagulant properties of bovine plasma protein C following activation by thrombin

Kisiel, Walter; Canfield, William M.; Ericsson, Lowell H.; Davie, Earl W.

doi:10.1021/bi00645a029

Cited by 493 publications

(206 citation statements)

References 37 publications

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“…1251-labeled fibrinogen was prepared by using the chloramine-T method (11,19 (20). The cells used for these studies had been passaged [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] …”

Section: Methodsmentioning

confidence: 99%

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Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity.

Sakata¹,

Curriden²,

Lawrence³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

181

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The effects of bovine activated protein C (APC) on the fibrinolytic activity of cultured bovine aortic endothelial cells were investigated. Confluent monolayers were incubated with purified APC under various conditions and changes in total fibrinolytic activity and in the level of plasminogen activator and plasminogen activator inhibitor (antiactivator) were monitored. The addition of APC to the cells in the absence of other blood or plasma components led to a rapid, dose-dependent increase of fibrinolytic activity both in the media and in cellular extracts. For example, 3.4 jtg of APC per ml resulted in a 15-fold increase of fibrinolytic activity in the medium within 1 hour. The enhanced fibrinolytic activity reflected increases in both the urokinase-related and tissue-type plasminogen activators produced by these cells. Interestingly, treatment of-cells with APC also caused a rapid, dose-dependent decrease in antiactivator activity. Diisopropyl fluorophosphate-inactivated APC did not decrease antiactivator or increase plasminogen activator. Although a small but significant direct (i.e., cell-independent) effect of APC on both fibrinolytic activity and antiactivator activity could be demonstrated, the major portion of these changes appeared to be cellmediated. These observations indicate that the fibrinolytic potential of cultured endothelial cells is increased by APC and that the enzyme active site is essential for this change. Moreover, the results suggest that one of the primary mechanisms for this stimulation of endothelial cell fibrinolytic activity involves an APC-mediated decrease in antiactivator.

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Section: Methodsmentioning

confidence: 99%

“…In addition to its well-documented anticoagulant activity (4)(5)(6), activated PC (APC) also exerts a potent profibrinolytic activity in vivo. For example, infusion of bovine APC into dogs results in increased circulating plasminogen activator (PA), presumably reflecting the release of this molecule from the endothelium (7,8).…”

mentioning

confidence: 99%

Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity.

Sakata¹,

Curriden²,

Lawrence³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

181

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“…EPCR facilitates the interaction of PC with the receptor complex of IIa:thrombomodulin (TM) on the endothelial cell surface, properly aligning PC with IIa [5]. IIa cleaves PC to generate activated protein C (APC) [6]. Once it releases from EPCR, APC will inactivate coagulation factors Va and VIIIa [7,8], in the presence of a cofactor, protein S (PS) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

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Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1-50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified "checkerboard" analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1.

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“…Prothrombin (factor II), factor VII, factor IX and factor X are the four traditional vitamin K-dependent clotting factors [ 11, whereas the fifth protein, called protein C [2] was isolated and characterized only recently . Evidence has been presented [7] indicating that protein C has a regulatory function in blood coagulation. Protein C can be activated to a serine amidase by the factor X activator from Russel's viper venom or by thrombin [3].…”

Section: Introductionmentioning

confidence: 99%

Protein S, a new vitamin K‐dependent protein from bovine plasma

Stenflo

Jönsson

1979

FEBS Letters

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Anticoagulant properties of bovine plasma protein C following activation by thrombin

Cited by 493 publications

References 37 publications

Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity.

Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity.

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Protein S, a new vitamin K‐dependent protein from bovine plasma

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