Reduction of von Willebrand Factor by Endothelial Cells

Xie, Lijuan; Chesterman, Colin N.; Hogg, Philip J.

doi:10.1055/s-0037-1614052

Cited by 37 publications

(41 citation statements)

References 21 publications

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“…Von Willebrand factor forms huge multimers connected via disulfide bonds. Its biological activity is known to depend on multimer size and reductase secreted from endothelial cells downsizes the multimer (37). Significant changes in multimer distributions of adiponectin with meals were not seen in our preliminary experiments, though Pajvani et al (29) recently reported a shift to smaller multimers to occur with insulin administration.…”

Section: Table IIIcontrasting

confidence: 57%

Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes

Waki

Yamauchi

Kamon

et al. 2003

Journal of Biological Chemistry

911

900

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Adiponectin is an adipocyte-derived hormone, which has been shown to play important roles in the regulation of glucose and lipid metabolism. Eight mutations in human adiponectin have been reported, some of which were significantly related to diabetes and hypoadiponectinemia, but the molecular mechanisms of decreased plasma levels and impaired action of adiponectin mutants were not clarified. Adiponectin structurally belongs to the complement 1q family and is known to form a characteristic homomultimer. Herein, we demonstrated that simple SDS-PAGE under non-reducing and non-heat-denaturing conditions clearly separates multimer species of adiponectin. Adiponectin in human or mouse serum and adiponectin expressed in NIH-3T3 or Escherichia coli formed a wide range of multimers from trimers to high molecular weight (HMW) multimers. A disulfide bond through an amino-terminal cysteine was required for the formation of multimers larger than a trimer. An amino-terminal Cys-Ser mutation, which could not form multimers larger than a trimer, abrogated the effect of adiponectin on the AMP-activated protein kinase pathway in hepatocytes. Among human adiponectin mutations, G84R and G90S mutants, which are associated with diabetes and hypoadiponectinemia, did not form HMW multimers. R112C and I164T mutants, which are associated with hypoadiponectinemia, did not assemble into trimers, resulting in impaired secretion from the cell. These data suggested impaired multimerization and/or the consequent impaired secretion to be among the causes of a diabetic phenotype or hypoadiponectinemia in subjects having these mutations. In conclusion, not only total concentrations, but also multimer distribution should always be considered in the interpretation of plasma adiponectin levels in health as well as various disease states.

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Section: Table IIIcontrasting

confidence: 57%

Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes

Waki

Yamauchi

Kamon

et al. 2003

Journal of Biological Chemistry

911

900

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“…15 Endothelial cells in culture secrete an activity that reduces the size of very large multimers of von Willebrand factor (VWF). 16 This activity appears to be independent of the proteolysis of VWF by ADAMTS13 and is inhibited by thiol blocking reagents. The VWF reductant secreted from endothelial cells has been identified as thrombospondin-1.…”

mentioning

confidence: 95%

Endothelium-derived but not platelet-derived protein disulfide isomerase is required for thrombus formation in vivo

Jasuja

Furie

2010

Blood

151

219

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Protein disulfide isomerase (PDI) catalyzes the oxidation reduction and isomerization of disulfide bonds. We have previously identified an important role for extracellular PDI during thrombus formation in vivo. Here, we show that endothelial cells are a critical cellular source of secreted PDI, important for fibrin generation and platelet accumulation in vivo. Functional PDI is rapidly secreted from human umbilical vein endothelial cells in culture upon activation with thrombin or after laser-induced stimulation. PDI is localized in different cellular compartments in activated and quiescent endothelial cells, and is redistributed to the plasma membrane after cell activation. In vivo studies using intravital microscopy show that PDI appears rapidly after laser-induced vessel wall injury, before the appearance of the platelet thrombus. If platelet thrombus formation is inhibited by the infusion of eptifibatide into the circulation, PDI is IntroductionA considerable body of evidence implicates the oxidation state of labile disulfide bonds in critical hemostatic proteins in regulating the process of thrombus formation. 1 The oxidation state of these bonds is regulated by an enzyme(s) of the thiol isomerase family. Thiol isomerases, including protein disulfide isomerase (PDI), while containing endoplasmic reticulum retention signals, are found extracellularly. Among the cells that secrete PDI and display the enzyme on their surface are platelets and endothelial cells. [2][3][4][5][6][7] The importance of thiol-disulfide balance for platelet function has long been recognized. For example, reduced glutathione and cysteine inhibit platelet aggregation induced by several agonists, while dithiothreitol and ␤-mercaptoethanol promote aggregation. 4 PDI likely plays an important role in maintaining this balance. The levels of both PDI and ERp5, another member of the PDI family, on the platelet surface increase significantly upon agonist stimulation. 4,6 PDI has been implicated in ␣ IIb ␤ 3 and ␣ 2 ␤ 1 activity, 8,9 and glycoprotein Ib ␣ expresses one or more free thiols on the activated platelet surface, but not on resting platelets. 4 Inhibitory anti-PDI antibodies or bacitracin, a nonspecific inhibitor of thiol isomerases, inhibit platelet activation in vitro, suggesting that ␣ IIb ␤ 3 -dependent platelet aggregation and secretion require thiol isomerases. 10 PDI may play a role in the de-encryption of tissue factor. [11][12][13] In contrast, there is less information to support potential roles of extracellular thiol isomerases in the function of endothelial cells. Endothelial cells in culture secrete PDI, which then is bound to the cell surface. 5 A novel thiol isomerase that appears to be endothelial cell specific, EndoPDI or ERp46, has been reported. 14 Recent evidence indicates that the protein disulfide isomerases, ERp46 and ERp57, are present in endothelial cell plasma membrane preparations. 15 Endothelial cells in culture secrete an activity that reduces the size of very large multimers of von Willebrand factor (VW...

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“…However this static view of the function of disulfide bonds has been challenged since the mid1990s by a steady increase of evidence for extracellular regulation due to disulfide cleavage. Examples include secreted proteins like thrombospondin-1 [122], von Willebrand factor [123,124] and plasmin [125], and cell surface receptors like the CD-4 T-cell receptor [126], integrins [127,128] and the HIV protein gp120 [129]. Extracellular redox regulation has also been suggested as essential in activation of Gprotein coupled receptors [130].…”

Section: Chemistry Controls Mechanics: Mechanochemical Switches In Thmentioning

confidence: 99%

The interplay between chemistry and mechanics in the transduction of a mechanical signal into a biochemical function

Valle¹,

Sandal²,

Samorı̀³

2007

Physics of Life Reviews

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Abstract:There are many processes in biology in which mechanical forces are generated. Force-bearing networks can transduce locally developed mechanical signals very extensively over different parts of the cell or tissues. In this article we conduct an overview of this kind of mechanical transduction, focusing in particular on the multiple layers of complexity displayed by the mechanisms that control and trigger the conversion of a mechanical signal into a biochemical function. Single molecule methodologies, through their capability to introduce the force in studies of biological processes in which mechanical stresses are developed, are unveiling subtle intertwining mechanisms between chemistry and mechanics and in particular are revealing how chemistry can control mechanics. The possibility that chemistry interplays with mechanics should be always considered in biochemical studies.

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Reduction of von Willebrand Factor by Endothelial Cells

Cited by 37 publications

References 21 publications

Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes

Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes

Endothelium-derived but not platelet-derived protein disulfide isomerase is required for thrombus formation in vivo

The interplay between chemistry and mechanics in the transduction of a mechanical signal into a biochemical function

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