The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Vance G Nielsen - One of the best experts on this subject based on the ideXlab platform.
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catroxmp ii a heme modulated fibrinogenolytic metalloproteinase isolated from Crotalus atrox venom
Biometals, 2018Co-Authors: Montamas Suntravat, Paul R Langlais, Elda E Sanchez, Vance G NielsenAbstract:It has been recently demonstrated that the hemotoxic venom activity of several species of snakes can be inhibited by carbon monoxide (CO) or a metheme forming agent. These and other data suggest that the biometal, heme, may be attached to venom enzymes and may be modulated by CO. A novel fibrinogenolytic metalloproteinase, named CatroxMP-II, was isolated and purified from the venom of a Crotalus atrox viper, and subjected to proteolysis and mass spectroscopy. An ion similar to the predicted singly charged m/z of heme at 617.18 was identified. Lastly, CORM-2 (tricarbonyldichlororuthenium (II) dimer, a CO releasing molecule) inhibited the fibrinogenolytic effects of CatroxMP-II on coagulation kinetics in human plasma. In conclusion, we present the first example of a snake venom metalloproteinase that is heme-bound and CO-inhibited.
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Crotalus atrox venom exposed to carbon monoxide has decreased fibrinogenolytic activity in vivo in rabbits
Basic & Clinical Pharmacology & Toxicology, 2018Co-Authors: Vance G NielsenAbstract:Envenomation by haemotoxic enzymes remains a significant source of human morbidity and mortality worldwide, with administration of long-acting or multiple doses of antivenom first-line therapy. However, coagulopathy can still occur and recur. Of interest, it has been recently demonstrated that direct, isolated exposure of snake venom enzymes with fibrinogenolytic activity to carbon monoxide (CO) abrogates venom-mediated loss of coagulation in human plasma. These observations of CO inhibition of venom fibrinogenolytic activity were subsequently repeated in rabbit whole blood. This study sought to translate these findings in an in vivo rabbit model of envenomation with fibrinogenolytic Crotalus atrox venom. Sedated rabbits were intravenously administered C. atrox venom (400 μg/kg) pre-exposed to 0 or 1000 μM carbon monoxide-releasing molecule-2 (CORM-2) in vitro. Arterial whole-blood samples demonstrated that compared to pre-envenomation values, the CORM-2-naive venom significantly prolonged the onset of coagulation, decreased the velocity of clot growth and decreased clot strength as determined by thromboelastography an hour after venom injection. In contrast, CORM-2 pre-exposure prevented or attenuated C. atrox venom effects on coagulation kinetics. Future studies to determine whether rabbits injected with such venom subcutaneously/intramuscularly can have consequent coagulopathy abrogated by injection of carbon monoxide-releasing molecules into the ‘bite site’ are justified.
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Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom
BioMetals, 2017Co-Authors: Christine S. Olver, Vance G NielsenAbstract:While the administration of antivenom to treat hemotoxic snake bite injury remains the gold standard of therapy, we have demonstrated that modifying human fibrinogen with iron and carbon monoxide renders it resistant to fibrinogenolytic snake venom enzymes. In order to translate these findings into a possible biometal-based therapy complementary to antivenom administration, a preclinical model that possesses fibrinogen that closely mimics the human molecule in response to iron and carbon monoxide needed to be identified. The goal of this investigation was to determine if a swine model could serve in this capacity by assessing the thrombelastographic response of porcine plasma to iron and carbon monoxide exposure, without or with further exposure to the fibrinogenolytic venom of the viper Crotalus atrox . Using plasma obtained from eight swine, it was determined that their plasma responded to iron and carbon monoxide in a manner similar to that of human plasma by displaying enhanced coagulation kinetics. However, in sharp contrast to the response seen with human plasma, only iron significantly protected porcine plasma coagulation kinetics from C. atrox venom degradation. Therefore the pig is an animal beyond humans that could derive benefit from the biometal-focused therapy of iron infusion to protect against venom mediated compromise of coagulation. Thus, future investigation to assess the effects of iron administration to attenuate the effects of fibrinogenolytic envenomation with a pig model is justified.
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iron and carbon monoxide attenuate degradation of plasmatic coagulation by Crotalus atrox venom
Blood Coagulation & Fibrinolysis, 2016Co-Authors: Vance G Nielsen, Leslie V BoyerAbstract:Hypofibrinogenemia is an important clinical consequence following envenomation by Crotalus species, usually attenuated or prevented by administration of antivenom. It has been determined that iron and carbon monoxide (CO) enhance fibrinogen as a thrombin substrate, likely secondary to conformational changes in molecular structure. We tested the hypothesis that pretreatment of plasma with iron and CO could attenuate the effects of exposure to Crotalus atrox venom. Human plasma was exposed to 0 to 10 μmol/l ferric chloride (iron source) and 0 to 100 μmol/l CO-releasing molecule-2 (CO source) followed by exposure to 0 to 0.5 μg/ml venom for 5 to 20 min. Changes in coagulation kinetics were determined with thrombelastography. Iron and CO significantly attenuated venom-mediated degradation of plasmatic coagulation in terms of onset time, velocity of clot growth and final clot strength. Further preclinical investigation of iron and CO administration as a 'bridge-to-antivenom' to preserve plasmatic coagulation is justified.
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iron and carbon monoxide attenuate Crotalus atrox venom enhanced tissue type plasminogen activator initiated fibrinolysis
Blood Coagulation & Fibrinolysis, 2016Co-Authors: Vance G Nielsen, Leslie V Boyer, Ryan W Matika, Quinlan Amos, Daniel T RedfordAbstract:In addition to degrading fibrinogen as a source of consumptive coagulopathy, rattlesnake venom has also been demonstrated to enhance fibrinolysis and degrade alpha-2-antiplasmin. The goals of this investigation was to characterize the kinetic fibrinolytic profile of Crotalus atrox venom in the absence and presence of tissue-type plasminogen activator (tPA), and to also ascertain if iron and carbon monoxide (CO, a positive modulator of alpha-2-antiplasmin) could attenuate venom-enhanced fibrinolysis. Utilizing thrombelastographic methods, the coagulation and fibrinolytic kinetic profiles of human plasma exposed to C. atrox venom (0-2 μg/ml) were determined in the absence or presence of tPA (0-100 IU/ml). Then, either separately or in combination, plasma was exposed to iron (ferric chloride, 10 μmol/l) or CO (carbon monoxide-releasing molecule-2, 100 μmol/l) prior to incubation with venom; the plasma sample was subsequently subjected to thrombelastographic analysis with addition of tPA. Venom exposure in the absence of tPA did not result in detectable fibrinolysis. In the presence of tPA, venom markedly enhanced fibrinolysis. Iron and CO, markedly attenuated venom enhancement of fibrinolysis. C. atrox venom enhances tPA-mediated fibrinolysis, and interventions that enhance/protect alpha-2-antiplasmin activity significantly attenuate venom-enhanced fibrinolysis. Future preclinical investigation is required to determine if iron and CO can attenuate venom-mediated degradation of alpha-2-antiplasmin-dependent fibrinolytic resistance.
Murray S Blum - One of the best experts on this subject based on the ideXlab platform.
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glycerol monoethers in the scent gland secretions of the western diamondback rattlesnake Crotalus atrox serpentes crotalinae
Cellular and Molecular Life Sciences, 1990Co-Authors: P J Weldon, H A Lloyd, Murray S BlumAbstract:1-O-Monoalkylglycerols with C12 to C20 chains were identified in the scent, gland secretions of the western diamondback rattlesnake (Crotalus atrox). This is the first documentation of these compounds in the skin secretions of a reptile.
P J Weldon - One of the best experts on this subject based on the ideXlab platform.
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glycerol monoethers in the scent gland secretions of the western diamondback rattlesnake Crotalus atrox serpentes crotalinae
Cellular and Molecular Life Sciences, 1990Co-Authors: P J Weldon, H A Lloyd, Murray S BlumAbstract:1-O-Monoalkylglycerols with C12 to C20 chains were identified in the scent, gland secretions of the western diamondback rattlesnake (Crotalus atrox). This is the first documentation of these compounds in the skin secretions of a reptile.
Kaifa Huang - One of the best experts on this subject based on the ideXlab platform.
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characterization of a protease with α and β fibrinogenase activity from the western diamondback rattlesnake Crotalus atrox
Biochemical and Biophysical Research Communications, 1992Co-Authors: Shyhhorng Chiou, Chinchun Hung, Kaifa HuangAbstract:A metalloprotease from the rattlesnake Crotalus atrox venom was isolated and purified from multiple-step chromatographies including anion-exchange chromatography, gel permeation and reversed-phase HPLC. The fraction was shown to be homogeneous as judged by SDS-gel electrophoresis. It also showed a high proteolytic activity against α- and β-chains of fibrinogen molecules. Further characterization of the purified fraction with fribrinogenase activity indicated that it is a single-chain protease with a molecular mass of about 24 kDa and an acidic isoelectric point. It is relatively heat stable up to about 65°C, inhibited by EDTA, β-mercaptoethanol, but not by phenylmethanesulfonyl fluoride, N α - p -tosyl- l -phenylalanine chloromethyl ketone and N α - p -tosyl- l -lysine chloromethyl ketone, soybean trypsin inhibitor and aprotinin. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to some metalloproteases characterized before from the closely related rattlesnake venoms. n -Terminal sequence analysis of the enzyme corroborated some similarity between this enzyme and the reported sequences of these enzymes characterized from the Crotalidae snake family. This study indicated the presence of a novel fibrinogenase (termed Catroxase) with n -terminal sequence different from the metalloprotease with hemorrhagic activity isolated from the same Western diamondback rattlesnake.
Shyhhorng Chiou - One of the best experts on this subject based on the ideXlab platform.
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characterization of a protease with α and β fibrinogenase activity from the western diamondback rattlesnake Crotalus atrox
Biochemical and Biophysical Research Communications, 1992Co-Authors: Shyhhorng Chiou, Chinchun Hung, Kaifa HuangAbstract:A metalloprotease from the rattlesnake Crotalus atrox venom was isolated and purified from multiple-step chromatographies including anion-exchange chromatography, gel permeation and reversed-phase HPLC. The fraction was shown to be homogeneous as judged by SDS-gel electrophoresis. It also showed a high proteolytic activity against α- and β-chains of fibrinogen molecules. Further characterization of the purified fraction with fribrinogenase activity indicated that it is a single-chain protease with a molecular mass of about 24 kDa and an acidic isoelectric point. It is relatively heat stable up to about 65°C, inhibited by EDTA, β-mercaptoethanol, but not by phenylmethanesulfonyl fluoride, N α - p -tosyl- l -phenylalanine chloromethyl ketone and N α - p -tosyl- l -lysine chloromethyl ketone, soybean trypsin inhibitor and aprotinin. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to some metalloproteases characterized before from the closely related rattlesnake venoms. n -Terminal sequence analysis of the enzyme corroborated some similarity between this enzyme and the reported sequences of these enzymes characterized from the Crotalidae snake family. This study indicated the presence of a novel fibrinogenase (termed Catroxase) with n -terminal sequence different from the metalloprotease with hemorrhagic activity isolated from the same Western diamondback rattlesnake.
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isolation of a crotalase like protease with alpha fibrinogenase activity from the western diamondback rattlesnake Crotalus atrox
Biochemistry international, 1992Co-Authors: Shyhhorng Chiou, Chinchun HungAbstract:Venom toxins were isolated from rattlesnake (Crotalus atrox) venom by cation-exchange chromatography. Seven major fractions could be obtained by single-step ion-exchange chromatography with two fractions showing essentially apparent homogeneity by SDS-gel electrophoresis. All fractions showed various extents of specific proteolytic activity against alpha- or beta-chains of fibrinogen molecules. Further characterization of one of the purified fractions with alpha-fribrinogenase activity indicated that it is a single-chain thrombin-like protease with a molecular mass of about 30 kDa. It is relatively heat stable, inhibited by phenylmethanesulfonyl fluoride, N alpha-p-tosyl-L-phenylalanine chloromethyl ketone and N alpha-p-tosyl-L-lysine chloromethyl ketone but not by soybean trypsin inhibitor and beta-mercaptoethanol. Amino acid analysis showed that the enzyme possesses an amino acid composition very similar to thrombin and crotalase characterized before from the closely related snake venoms. N-Terminal sequence analysis of the enzyme corroborated the close similarity between this enzyme and those sequences of crotalase and kallikrein-like enzymes characterized from the same Crotalidae snake family. This study is in contrast to the previous reports which indicated a lack of thrombin- and crotalase-like enzyme in the venom of Western diamondback rattlesnake.