Assembly, activation, and physiologic influence of the plasma kallikrein/kinin system

Schmaier, Alvin H.

doi:10.1016/j.intimp.2007.08.022

Cited by 81 publications

(76 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, FXII activation is greatly enhanced in the presence of dextran sulfate, suggesting that negatively charged protein aggregates are better contact system-activating surfaces (13). Based upon these established facts (41) and our data (Fig. 1), we propose that the contact system is a broad pattern recognition system, recognizing negative charges rather than specific chemical structures.…”

Section: Discussionsupporting

confidence: 73%

“…Contact System Is a Pattern Recognition System-It has been reported that in vitro contact system activation occurs on physiologically relevant surfaces such as articular cartilage, skin, sodium urate crystals, and calcium pyrophosphate (41). In vivo contact system activation occurs on developing thrombus, RNA and DNA from degrading cells, enriched polysomes from platelet membranes, ␤-amyloid, sulfatides, fatty acids, cholesterol sulfate, GAGs, activated platelet surface during platelet transfusion (42), ionic contrast media (43), and also under conditions of sepsis, where bacteria lipopolysaccharides provide a negatively charged surface (44 -47).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Pan

Qian

Zhou

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Contaminated heparin was associated with adverse reactions by activating the contact system. Chemically oversulfated/modified glycosaminoglycans (GAGs) consisting of heparan sulfate, dermatan sulfate, and chondroitin sulfate have been identified as heparin contaminants. Current studies demonstrated that each component of oversulfated GAGs was comparable with oversulfated chondroitin sulfate in activating the contact system. By testing a series of unrelated negatively charged compounds, we found that the contact system recognized negative charges rather than specific chemical structures. We further tested how oversulfated GAGs and contaminated heparins affect different cell signaling pathways. Our data showed that chemically oversulfated GAGs and contaminated heparin had higher activity than the parent compounds and authentic heparin, indicative of sulfation-dominant and GAG sequencedependent activities in BaF cell-based models of fibroblast growth factor/fibroblast growth factor receptor, glial cell linederived neurotrophic factor/c-Ret, and hepatocyte growth factor/c-Met signaling. In summary, these data indicate that contaminated heparins intended for blood anticoagulation not only activated the contact system but also modified different GAGdependent cell signaling pathways.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Pan

Qian

Zhou

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Chymase, chymotrypsin-like, cathepsin A, B, D, and G involvement was excluded because 100 M of the serine protease inhibitor chymostatin inhibited NPY 3-36 degradation only by 32%. We then chose the serine protease inhibitor gabexate mesylate (29,30), an antithrombotic agent able to inhibit several proteases involved in multiple proteolytic systems in plasma, including the classic complement pathway, plasmin, and kallikrein in the fibrinolytic pathway, and the activation of factor IX in the coagulation cascade (31,32). A dose-dependent inhibition of NPY production was observed with gabexate mesylate from Table 1.…”

Section: Determination Of the Kinetic Constants Of Dppiv And Amp On Nmentioning

confidence: 99%

Kinetic Study of Neuropeptide Y (NPY) Proteolysis in Blood and Identification of NPY3–35

Abid¹,

Rochat

Lassahn

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

There is little information on how neuropeptide Y (NPY) proteolysis by peptidases occurs in serum, in part because reliable techniques are lacking to distinguish different NPY immunoreactive forms and also because the factors affecting the expression of these enzymes have been poorly studied. In the present study, LC-MS/MS was used to identify and quantify NPY fragments resulting from peptidolytic cleavage of NPY Neuropeptide Y (NPY)2 is a 36-amino acid peptide involved in the central and peripheral control of blood pressure (1-4) and in feeding behavior and obesity (5-9). NPY stimulates at least 6 types of receptors, called Y1, Y2, Y3, Y4, Y5, and y6 (10 -12). The Y1 receptor has high affinity for full-length NPY, while Y2 and Y5 receptors bind and are stimulated by fulllength and N-terminally truncated NPY. The physiological effects associated to the Y1 and Y2 receptors are the best known; exposure to a Y1 agonist causes an increase in blood pressure and potentiates postsynaptically the action of other vasoactive substances (1, 4, 13), whereas Y2 receptors are mainly located presynaptically, and upon stimulation mediate the inhibition of neurotransmitter release (14,15). NPY is a prototype of peptide whose function can be altered by proteases. Among peptidases displaying a high affinity for NPY, the primary role appears to be played by dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5), a serine-type protease, also known as CD26, that releases an N-terminal dipeptide, Xaa-Xab--Xac, preferentially when Xab is a proline or an alanine residue (16). By cleaving the Tyr-Pro dipeptide off the NPY N-terminal extremity, DPPIV generates NPY 3-36 , a truncated form that loses its affinity for the Y1 receptor and becomes a Y2/Y5 receptor agonist (17, 18).NPY can also be degraded by aminopeptidase P (AmP, EC 3.4.11.9), a metalloprotease that hydrolyzes the peptide bond between the first and the second amino acid residue at the N terminus of proteins, if the second amino acid is a proline (19). AmP removes the N-terminal tyrosine from NPY to generate NPY 2-36 , a selective Y2 agonist (18,20). There is little information on how NPY cleavage by these enzymes occurs in serum, in part because reliable techniques are lacking to distinguish different NPY immunoreactive (NPYir) forms and also because the factors affecting the expression of these enzymes have been poorly studied. Recently, Frerker et al. (21) reported by MALDI-TOF mass spectrometry that NPY 1-36 is exclusively degraded by DPPIV into NPY 3-36 in EDTA-plasma but they did not provide kinetics of NPY cleavage efficiency of DPPIV. BeckSickinger and co-workers (22) studied with the same technique the metabolic stability of fluorescent N-terminally labeled NPY analogues incubated in human plasma and found that the 36th, 35th, and 33rd residues of NPY analogues may also be removed by unknown carboxypeptidases.We have set up a method using liquid chromatography coupled with tandem mass spectrometry (LC-MS n ) to selectively quantify NPY and its C-terminal fragments NPY 2-36 an...

show abstract

“…FXIa generated through this loop further enhances thrombin generation, leading to a faster and more stable thrombus formation. FXIIa deficiency has been shown to be associated with a prolonged activated Partial Thromboplastin Time (aPTT), suggesting that FXII has a useful predictive value of the vascular blood flow [14]. Although FXII was considered to have a major role in the activation of the fibrinolytic pathway, recent reports indicate that its role may be limited [15].…”

Section: Introductionmentioning

confidence: 99%

Physiological Effects of the Plasma Kallikrein-Kinin System: Roles of the Blood Coagulation Factor XII (Hageman Factor)

Lynch¹,

Shariat‐Madar²

2012

J Clin Toxicol

View full text Add to dashboard Cite

For many decades the intrinsic coagulation research has focused on factor XII (Hageman factor; FXII) and its significant role as a sole instigating factor driving the stabilization of thrombotic clotting. FXII is a relatively weak risk factor for thrombosis although its amidolytic and proteolytic function renders its presence important. Accumulating evidence suggests that FXII is pivotally involved in pathologic coagulation. In particular, the role of FXII in initiation and propagation of the blood coagulation and fibrinolytic systems has impeccable scientific support to the extent of which the existence of a "FXII-dependent pathway of thrombosis" is now generally accepted. The concept, although not a new one to scientists in the field of coagulation, is a caveat to the pathologic clot forming FXII concept in that it appears to cause a conceptual shift in de-emphasizing the inherent complexity of FXII activation representing a spectrum of responses. For instance, FXII contributes to the activation of inflammation and complement systems and influences catecholamine release from the adrenal system, suggesting that FXII can trigger multiple signaling pathways upon activation. The nature and duration of each of the FXII-dependent pathways may depend not only on the kind of stimulus, but also it may have distinct response pattern under normal and pathophysiologic conditions.Because a plethora of pathophysiological pathways are influenced by FXII, additional studies into its role as an important first step behind regulating common daily stresses may promise to provide new insight to better understand the unique and subtle biology behind FXII.

show abstract

Assembly, activation, and physiologic influence of the plasma kallikrein/kinin system

Cited by 81 publications

References 59 publications

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Kinetic Study of Neuropeptide Y (NPY) Proteolysis in Blood and Identification of NPY3–35

Physiological Effects of the Plasma Kallikrein-Kinin System: Roles of the Blood Coagulation Factor XII (Hageman Factor)

Contact Info

Product

Resources

About