Characterization of snake venom components acting on blood coagulation and platelet function

Ouyang, Chaoho; Teng, Che-Ming; Huang, Tur‐Fu

doi:10.1016/0041-0101(92)90040-c

Cited by 131 publications

(67 citation statements)

References 140 publications

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“…All sPLA 2 s have a common active site but may possess distinct pharmacological sites, explaining the diversity of pharmacological effects of venom sPLA 2 s, such as neurotoxicity, myotoxicity, cardiotoxicity, inhibition or potentiation of platelet aggregation, and anticoagulant action (25,26). In particular, all venom anticoagulant sPLA 2 s have a basic pI correlated with the presence of basic amino acids located between residues 50 and 80 which may be involved in the anticoagulant effect of venom sPLA 2 in addition to the lipolytic activity (27,28).…”

mentioning

confidence: 99%

Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

Mounier¹,

Hackeng²,

Schaeffer³

et al. 1998

Journal of Biological Chemistry

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Human group II secretory phospholipase A 2 (hsPLA 2 ) exhibits significant anticoagulant activity that does not require its enzymatic activity. We examined which coagulation factor was targeted by hsPLA 2 and analyzed which region of the protein may be involved in this inhibition. Prothrombin time coagulation assays indicated that hsPLA 2 did not inhibit activated factor V (FVa) activity, whereas activated factor X (FXa) onestage coagulation assays suggested that FXa was inhibited. The inhibitory effect of hsPLA 2 on prothrombinase activity of FXa, FV, phospholipids, and Ca 2؉ complex was markedly enhanced upon preincubation of hsPLA 2 with FXa but not with FV. Prothrombinase activity was also strongly inhibited by hsPLA 2 in the absence of PL. High concentrations of FVa in the prothrombinase generation assay reversed the inhibitory effect of hsPLA 2 . By using isothermal titration calorimetry, we demonstrated that hsPLA 2 binds to FXa in solution with a 1:1 stoichiometry and a K d of 230 nM. By using surface plasmon resonance we determined the rate constants, k on and k off , of the FXa/hsPLA 2 interaction and analyzed the Ca 2؉ effect on these constants. When preincubated with FXa, synthetic peptides comprising residues 51-74 and 51-62 of hsPLA 2 inhibited prothrombinase assays, providing evidence that this part of the molecule, which shares similarities with a region of FVa that binds to FXa, is likely involved in the anticoagulant interaction of hsPLA 2 with FXa. In conclusion, we propose that residues 51-62 of hsPLA 2 bind to FXa at a FVa-binding site and that hsPLA 2 decreases the prothrombinase generation by preventing FXa⅐FVa complex formation.

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mentioning

confidence: 99%

Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

Mounier¹,

Hackeng²,

Schaeffer³

et al. 1998

Journal of Biological Chemistry

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“…[10,11] Toxins can cause diverse systemic effects, such as leukocytosis, thrombocytopenia, hypofibrinogenemia, bleeding disorders, proteinuria, and azotemia. [4,12,13] However, leukocytosis has been primarily reported as a laboratory finding.…”

Section: Discussionmentioning

confidence: 99%

The Evaluation of Snake Bite Cases Applied to Emergency Department: 132 cases

Şahan

Taşın

Karakuş

et al. 2016

Ulus Travma Acil Cerrahi Derg

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“…As the majority of these enzymes are also known to hydrolyze the α-chain of fibrinogen (α-fibrinogenases; 37), and since fibrinogen is an important cofactor in platelet aggregation (38,39), it has been proposed that the inhibition of platelet aggregation caused by these enzymes is due to degradation of fibrinogen (2,40). However, we have shown that the proteolysis by jararhagin of the C-terminal fibrinogen α-chain, which contains an RGD sequence, does not affect fibrinogen-dependent platelet aggregation (41).…”

Section: Venom MDC Enzymes and Platelet Functionmentioning

confidence: 99%

“…As a result, it is common to find consumption of clotting factors and blood incoagulability accompanied by hemorrhage in victims of snakebite. Various reviews on this subject have been published (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Snake venom metalloproteinases and disintegrins: interactions with cells

Kamiguti

Zuzel

Theakston

1998

Braz J Med Biol Res

103

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Metalloproteinases and disintegrins are important components of most viperid and crotalid venoms. Large metalloproteinases referred to as MDC enzymes are composed of an N-terminal Metalloproteinase domain, a Disintegrin-like domain and a Cys-rich C-terminus. In contrast, disintegrins are small non-enzymatic RGD-containing cysteine-rich polypeptides. However, the disintegrin region of MDC enzymes bears a high degree of structural homology to that of the disintegrins, although it lacks the RGD motif. Despite these differences, both components share the property of being able to recognize integrin cell surface receptors and thereby to inhibit integrin-dependent cell reactions. Recently, several membrane-bound MDC enzymes, closely related to soluble venom MDC enzymes, have been described in mammalian cells. This group of membrane-anchored mammalian enzymes is also called the ADAM family of proteins due to the structure revealing A Disintegrin And Metalloproteinase domains. ADAMs are involved in the shedding of molecules from the cell surface, a property which is also shared by some venom MDC enzymes.

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Characterization of snake venom components acting on blood coagulation and platelet function

Cited by 131 publications

References 140 publications

Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

The Evaluation of Snake Bite Cases Applied to Emergency Department: 132 cases

Snake venom metalloproteinases and disintegrins: interactions with cells

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