The coagulation cascade: initiation, maintenance, and regulation

Davie, Earl W.; Fujikawa, Kazuo; Kisiel, Walter

doi:10.1021/bi00107a001

Cited by 1,762 publications

(1,389 citation statements)

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“…However, when exposed to thrombin, cytokines, or LPS, endothelial cells synthesize and express tissue factor at their surface (Nawroth et al, 1986;Mackman, 1997). Once coagulation has been initiated, endothelial cells promote thrombi activation since the activity of factor Xa (generated by tissue factor plus factor VII) is locally enhanced by promotion of binding with its cofactor Va at adjacent Xa and Va receptors on the endothelial cell surface (Davie et al, 1991;Chen et al, 2001). At the same time, levels of thrombomodulin are decreased.…”

Section: Coagulation and Fibrinolysismentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

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Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

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Section: Coagulation and Fibrinolysismentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

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“…Measurement of PT usually reflects the integrity of other haemostatic factors such as FXa, FVa and FIV [29]. As it was anticipated, PT concomitantly increased with the progression of liver failure.…”

Section: Discussionmentioning

confidence: 93%

Monitoring Coagulation Proteins During Progression of Liver Disease

et al. 2014

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This work was designated to monitor the coagulation abnormalities associated with the gradual progression of liver diseases. The study included fifty patients; forty were diagnosed with liver cirrhosis with different stages categorized according to the Childs-Pugh classification and another ten patients were diagnosed with hepatocellular carcinoma (HCC). Haemostatic variables including fibrinogen (FI), calcium (FIV), transglutaminase (FXIII), prothrombin time (PT) and platelet count were estimated in patients and compared with the baseline levels of healthy subjects (n = 10). The results demonstrated that the fibrinogen level was progressively decreased, whereas PT was progressively prolonged in Child A, Child B and Child C groups. The maximum deterioration was observed in HCC patients. Calcium significantly increased in mild (Child A) and moderate (Child B) but not in Child C cirrhosis and HCC patients. FXIII level did not show any significant changes in cirrhotic patients compared to healthy group. Some of the haemostatic variables we investigated were correlated with serum albumin and bilirubin but not with aminotransferases (ALT and AST). The results indicated that the haemostatic abnormalities in fibrinogen, calcium and PT (but not FXIII) were deteriorated in parallel with the gradual regression of the constitutional function of liver.

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“…Moreover, it exploits the unique properties of certain proteins that require a free N terminus for activity. In nature, some proteins are synthesized as inactive precursors, requiring proteolytic cleavage to become active; for example, zymogens undergo cleavage and activation in settings as diverse as blood coagulation and fibrinolysis [30], sodium balance and blood pressure [31], and apoptosis [32]. Cleavage of inactive precursors could generate a positive signal based on the measurable property, catalytic or otherwise, of the released protein.…”

Section: Nih Public Accessmentioning

confidence: 99%

Small ubiquitin-like modifying protein isopeptidase assay based on poliovirus RNA polymerase activity

Arnold

Bernal

Uche

et al. 2006

Analytical Biochemistry

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The ubiquitin-proteasome pathway is the major nonlysosomal proteolytic system in eukaryotic cells responsible for regulating the level of many key regulatory molecules within the cells. Modification of cellular proteins by ubiquitin and ubiquitin-like proteins, such as small ubiquitin-like modifying protein (SUMO), plays an essential role in a number of biological schemes, and ubiquitin pathway enzymes have become important therapeutic targets. Ubiquitination is a dynamic reversible process; a multitude of ubiquitin ligases and deubiquitinases (DUBs) are responsible for the wide-ranging influence of this pathway as well as its selectivity. The DUB enzymes serve to maintain adequate pools of free ubiquitin and regulate the ubiquitination status of cellular proteins. Using SUMO fusions, a novel assay system, based on poliovirus RNA-dependent RNA polymerase activity, is described here. The method simplifies the isopeptidase assay and facilitates high-throughput analysis of these enzymes. The principle of the assay is the dependence of the viral polymerase on a free N terminus for activity; accordingly, the polymerase is inactive when fused at its N terminus to SUMO or any other ubiquitin-like protein. The assay is sensitive, reproducible, and adaptable to a highthroughput format for use in screens for inhibitors/activators of clinically relevant SUMO proteases and deubiquitinases. Keywords Isopeptidases; Protein degradation; N terminus; 3D polymeraseThe ubiquitin-proteasomal pathway regulates the cellular content and/or compartmentalization of many proteins [1,2] and is a promising, albeit underexploited, area for drug discovery. The therapeutic value of this pathway was recently validated by the introduction and clinical success of Velcade, a proteasome inhibitor, for the treatment of refractory relapsed multiple myeloma [3]. Other ubiquitin-like proteins (UBLs) 1 have recently been shown to contribute similarly to the cellular regulation of proteins, with the most extensively characterized UBL being small ubiquitin-like modifying protein (SUMO) [4].Destruction of a targeted protein via the ubiquitin system initially involves recognition by a multienzyme system that attaches ubiquitin to the target protein. Energy is required to activate ubiquitin at its carboxy terminus. Activation is catalyzed by the enzyme E1, which links the ubiquitin C terminus to a cysteine side chain of the enzyme. This activated ubiquitin is * Corresponding author. Fax: +1 610 644 8616., E-mail address: mattern@progenra.com (M.R. Mattern).. 1 Abbreviations used: UBL, ubiquitin-like protein; SUMO, small ubiquitin-like modifying protein; UBP/USP, ubiquitin-specific protease; UCH, ubiquitin terminal hydrolase; DUB, deubiquitinating enzyme; Ub-AMC, Ub-7-amino-4-methylcoumarin; EDTA, ethylenediaminetetraacetic acid; IPTG, isopropyl-β-D-thiogalactopyranoside; PMSF, phenylmethylsulfonylfluoride; GFP, green fluorescent protein; DTT, dithiothreitol. transferred to a second enzyme of the series, E2 (ubiquitin-conjugating protein), as a thioe...

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The coagulation cascade: initiation, maintenance, and regulation

Abstract: ere are two principal mechanisms to stop the loss of blood in higher organisms following vascular injury. Initially, platelets are activated and adhere to the site of injury. The platelets then aggregate and form a platelet plug that reduces or tem-

Cited by 1,762 publications

References 117 publications

Endothelial cell functions

Endothelial cell functions

Monitoring Coagulation Proteins During Progression of Liver Disease

Small ubiquitin-like modifying protein isopeptidase assay based on poliovirus RNA polymerase activity

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