Some molecular and functional changes in high molecular weight kininogen induced by plasmin and trypsin

Kleniewski, J; Donaldson, Virginia H.; Wagner, Constance

doi:10.1016/0049-3848(82)90129-3

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…Plasmin has a relatively small trigger-indepen dent capacity to generate bradykinin from kininogens, 57,161 the main effect follows plasmin-induced kallikrein formation. 12 The clot-promoting activity of human HMr kininogen is only slightly decreased by plasmin digestion, 92 but this is different for bovine HMr kininogen. 185 The generation of brady kinin by plasmin may become manifest during thrombolytic therapy with streptokinase and uro kinase associated with large plasmin formation (see Migne et al 130 and references therein).…”

Section: Plasmatic Enzymesmentioning

confidence: 99%

Role of the Contact System in Fibrinolysis

Kluft¹,

Dooijewaard²,

Emeis³

1987

Semin Thromb Hemost

154

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Section: Plasmatic Enzymesmentioning

confidence: 99%

Role of the Contact System in Fibrinolysis

Kluft¹,

Dooijewaard²,

Emeis³

1987

Semin Thromb Hemost

154

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“…HK is cleaved by several proteinases, such as KK (15), FXIIa (16), FXIa (17), plasmin (18) and neutrophil elastase (19). KK liberates the potent vasoactive nonapeptide bradykinin by proteolytic cleavage at two sites (6), Lys 362 -Arg 363 and Arg 371 -Ser 372 , thereby transforming single-chain HK into a two-chain molecule consisting of a heavy chain (62 kDa) and a disulfide-linked light chain (61 kDa) (12,15).…”

Section: Introductionmentioning

confidence: 99%

High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326

Mauron¹,

Lämmle²,

Wuillemin³

2000

Thromb Haemost

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SummaryWe investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligandblotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels. Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326.In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.

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“…Furthermore, using Ca 2z as the marker of platelet activation, they show that preincubation of plasmin with platelets impaired the cytosolic increase of Ca 2z concentrations triggered by thrombin [24]. Thus, because plasmin, a serine protease with KAL enzymatic characteristics [30], desensitizes the thrombin-induced platelet activation and aggregation by a mechanism involving proteolytic truncation of PAR1, it seems reasonable to assume that proteolytic cleavage of PAR1 by KAL might have played an important role in the inhibition of the platelet aggregation seen in our work. The use of activating peptides such as SFLLRN and TR78 will be useful not only to investigate the possible mechanism of KALmediated inhibition of PAR-1 cleavage, but also to investigate whether, like plasmin [24], high KAL concentrations activate platelets by cleaving the thrombin site on PAR1 (the R 41 -S 42 peptide bond).…”

Section: Discussionmentioning

confidence: 97%

Thrombin‐stimulated platelet aggregation is inhibited by kallikrein in a time‐ and concentration‐dependent manner

Veloso

2003

Scandinavian Journal of Clinical and Laboratory Investigation

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Many in vitro studies have shown that activation of prekallikrein (PK) to kallikrein (KAL) in normal plasma triggers rapid activation of the coagulation cascade. In agreement, the coagulation activation is impaired in PK-deficient plasma. Paradoxically, PK-deficient patients show a tendency to thrombosis. To investigate the discrepancy between the in vitro and in vivo findings, we analyzed the effect of KAL on the rate of platelet aggregation. For this research, physiologic concentrations of washed human platelets were incubated for 5 and/or 10 min with approximately 2.2 to 88 nM human plasma KAL (< 1/100 to approximately 1/3 of PK concentrations in plasma) prior to the addition of high concentrations of alpha-thrombin (54 nM) or fibrinogen plus ADP. KAL concentrations were arbitrarily selected on the assumption that concentrations of free KAL (the enzymatically active species) were minute in normal plasma and higher when KAL production was enhanced, and/or inhibitors were depleted. Full platelet aggregation was that seen in the absence of KAL or PK. Inhibition of platelet aggregation stimulated by thrombin was markedly increased with increased KAL concentrations and incubation times. The degree of inhibition by KAL was smaller when ADP was the agonist. The data suggest that KAL may play a role in the modulation of platelet aggregation in vivo under normal conditions as well as when prolonged, high concentrations of KAL occur in blood. The data may also help to explain the intriguing observation that PK-deficient patients show a tendency to thrombotic episodes and myocardial infarction whereas in vitro assays predict bleeding.

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Some molecular and functional changes in high molecular weight kininogen induced by plasmin and trypsin

Cited by 8 publications

References 19 publications

Role of the Contact System in Fibrinolysis

Role of the Contact System in Fibrinolysis

High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326

Thrombin‐stimulated platelet aggregation is inhibited by kallikrein in a time‐ and concentration‐dependent manner

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