Bothrops jararaca fibrinogen and its resistance to hydrolysis evoked by snake venoms

Author(s):  
Carolina O. Vieira ◽  
Aparecida S. Tanaka ◽  
Ida S. Sano-Martins ◽  
Karen B. Morais ◽  
Marcelo L. Santoro ◽  
...  
1937 ◽  
Vol 65 (5) ◽  
pp. 613-639 ◽  
Author(s):  
Harry Eagle

Nine of the 17 venoms here tested were found capable of coagulating citrated blood or plasma. As has been believed by most workers in the field, 7 of these 9 coagulant venoms convert fibrinogen to an insoluble modification resembling fibrin (Bothrops atrox, Bothrops jararaca, Bothrops nummifera, Crotalus adamanteus, Crotalus horridus, Crotalus terrificus basiliscus, Crotalus terrificus terrificus). The optimum pH for this coagulation was determined for 3 of these, and was found in each case to be approximately pH 6.5, the same as that for the action of thrombin on fibrinogen. Unlike thrombin, however, the fibrinogen-coagulating activity of the venoms was unaffected by the antithrombin elaborated in the course of anaphylactic shock. In addition to coagulating fibrinogen directly, 3 of these venoms (Bothrops atrox, Bothrops jararaca, and to a less extent, Crotalus terrificus basiliscus) acted on prothrombin to convert it to thrombin, without the necessary intervention of either calcium or platelets. Finally, 2 venoms (Notechis scutatus, and to a slight extent, a mixed Micrurus venom), which had no demonstrable effect on purified fibrinogen, nevertheless converted prothrombin to thrombin. Unlike the reaction between the venoms and fibrinogen, this activation of prothrombin has no definite pH optimum, but takes place over a wide zone (pH 5.6–8.3). In the case of Bothrops atrox, there was some indication that the initial velocity of the reaction increased with increasing alkalinity, but that the amount of thrombin ultimately formed decreased. Extraordinarily minute quantities of some of these venoms sufficed to produce a demonstrable activation of prothrombin. Thus, the fer de lance (Bothrops atrox) venom was active in a 1:25,000,000 dilution, and that of the Australian tiger snake (Notechis scutatus) was active in a 1:4,000,000 dilution. The thrombin formed was indistinguishable from that produced by the action of calcium + platelets on prothrombin. Like the latter type of thrombin, and unlike venoms which act directly on fibrinogen, thrombin formed from prothrombin by venom was inhibited by antithrombin. Every one of the 9 non-coagulant venoms in this series destroyed prothrombin; and 5 of these destroyed fibrinogen as well. As is discussed in the text, there is reason to believe that these several properties of the venoms (coagulation and destruction of fibrinogen; activation and destruction of prothrombin) depend on the proteolytic enzymes which they were found to contain. These observations lend further support to the thesis that, in the course of physiological coagulation, (a) calcium plus platelets (or tissue derivative) constitute an enzyme system which reacts with prothrombin to form thrombin, and which is thus analogous to trypsin and to several of the proteolytic venoms here discussed, and (b) the thrombin so formed is itself a proteolytic enzyme which, like papain and the majority of the coagulant and proteolytic snake venoms here studied, reacts with fibrinogen to form a fibrillar gel, fibrin.


Toxicon ◽  
2012 ◽  
Vol 60 (2) ◽  
pp. 134-135
Author(s):  
Luana V. Senise ◽  
Sâmella S. Oliveira ◽  
Marcio Y. Yano ◽  
Savio S. Sant'Anna ◽  
Marcelo L. Santoro ◽  
...  

Toxins ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 69 ◽  
Author(s):  
Carolina Nicolau ◽  
Alyson Prorock ◽  
Yongde Bao ◽  
Ana Neves-Ferreira ◽  
Richard Valente ◽  
...  

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.


Toxicon ◽  
2001 ◽  
Vol 39 (10) ◽  
pp. 1505-1513 ◽  
Author(s):  
Stella R Zamuner ◽  
José Maria Gutiérrez ◽  
Marcelo N Muscará ◽  
Simone A Teixeira ◽  
Catarina F.P Teixeira

Toxicon ◽  
2000 ◽  
Vol 38 (9) ◽  
pp. 1253-1266 ◽  
Author(s):  
Vera L. Petricevich ◽  
Catarina F.P. Teixeira ◽  
Denise V. Tambourgi ◽  
José Marı́a Gutiérrez

Toxins ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 158 ◽  
Author(s):  
Karla Soares ◽  
Fiamma Gláucia-Silva ◽  
Alessandra Daniele-Silva ◽  
Manoela Torres-Rêgo ◽  
Nathália Araújo ◽  
...  

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 865
Author(s):  
Lilian Rumi Tsuruta ◽  
Ana Maria Moro ◽  
Denise V. Tambourgi ◽  
Osvaldo Augusto Sant’Anna

Oral tolerance is defined as a specific suppression of cellular and humoral immune responses to a particular antigen through prior oral administration of an antigen. It has unique immunological importance since it is a natural and continuous event driven by external antigens. It is characterized by low levels of IgG in the serum of animals after immunization with the antigen. There is no report of induction of oral tolerance to Bothrops jararaca venom. Here, we induced oral tolerance to B. jararaca venom in BALB/c mice and evaluated the specific tolerance and cross-reactivity with the toxins of other Bothrops species after immunization with the snake venoms adsorbed to/encapsulated in nanostructured SBA-15 silica. Animals that received a high dose of B. jararaca venom (1.8 mg) orally responded by showing antibody titers similar to those of immunized animals. On the other hand, mice tolerized orally with three doses of 1 µg of B. jararaca venom showed low antibody titers. In animals that received a low dose of B. jararaca venom and were immunized with B. atrox or B. jararacussu venom, tolerance was null or only partial. Immunoblot analysis against the venom of different Bothrops species provided details about the main tolerogenic epitopes and clearly showed a difference compared to antiserum of immunized animals.


2012 ◽  
Vol 6 (3) ◽  
pp. e1554 ◽  
Author(s):  
André Zelanis ◽  
Débora Andrade-Silva ◽  
Marisa M. Rocha ◽  
Maria F. Furtado ◽  
Solange M. T. Serrano ◽  
...  

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