Elevated plasma levels of hepatocyte growth factor in rats experimentally envenomated with Bothrops jararaca venom: role of snake venom metalloproteases

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dc.contributorLab. Farmacologiapt_BR
dc.contributorLab. Fisiopatologiapt_BR
dc.contributor.authorPrezoto, Benedito Carlospt_BR
dc.contributor.authorKato, Ellen Emipt_BR
dc.contributor.authorGonçalves, Luis Roberto de Camargopt_BR
dc.contributor.authorSampaio, Sandra Coccuzzopt_BR
dc.contributor.authorSano-Martins, Ida Siguekopt_BR
dc.date.accessioned2020-07-09T21:23:15Z-
dc.date.available2020-07-09T21:23:15Z-
dc.date.issued2019pt_BR
dc.identifier.citationPrezoto BC, Kato EE, Gonçalves LRC, Sampaio SC, Sano-Martins IS. Elevated plasma levels of hepatocyte growth factor in rats experimentally envenomated with Bothrops jararaca venom: role of snake venom metalloproteases. Toxicon. 2019 Apr;162:9-14. doi:10.1016/j.toxicon.2019.03.003.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2695-
dc.description.abstractThe hepatocyte growth factor (HGF)/c-met pathway, which mainly consists of HGF activator (HGFA) and its substrate HGF, protects various types of cells via anti-apoptotic and anti-inflammatory signals. Thrombin is the main physiological activator of such plasmatic pathway, and increased plasma concentrations of HGF have been considered as a molecular marker for some pathological conditions, such as disseminated intravascular coagulation. Since thrombin generation is often linked to tissue injury, and these events are common during snake venom-induced consumption coagulopathies (VICC), our goals were to examine whether Bothrops jararaca venom (Bjv), which induces VICC in vivo: (i) activates the HGF/c-met pathway in vivo and (ii) cleaves zymogen forms of HGFA and HGF (proHGFA and proHGF, respectively) in vitro. Two experimental groups (n = 6, each) of male adult Wistar rats were subcutaneously injected with 500?µL of 0.9% NaCl solution (control) or sub-lethal doses (1.6 mg/kg) of Bjv. Three hours after envenomation, whole blood samples were collected from the carotid arteries to evaluate relevant coagulation parameters using rotational thromboelastometry and fibrinogen level (colorimetric assay). Additionally, the plasma concentration of HGF was assayed (ELISA). Thromboelastometric assays showed that blood clotting and fibrin polymerization were severely impaired 3 h after Bjv injection. Total plasma HGF concentrations were almost 6-fold higher in the Bjv-injected group (410.0 ± 91) compared with control values (68 ± 18 pg/mL, p < 0.05). Western blotting assay showed that Bjv processed proHGFA and proHGF, generating bands resembling those generated by thrombin and kallikrein, respectively. In contrast to the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF), the metalloprotease inhibitor ethylenediaminetetraacetic acid disodium salt (Na2-EDTA) strongly reduced the ability of Bjv to process proHGFA and generated one active band similar to that of thrombin. Since Bjv contains prothrombin and factor X activators, increased intravascular thrombin formation might partly explain the increased HGF levels after bothropic envenomation. In conclusion, these findings suggest that snake venom metalloproteases may be determinant for elevation of plasma levels of HGF in rats experimentally envenomated with Bjv.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.format.extentp. 9-14pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofToxiconpt_BR
dc.titleElevated plasma levels of hepatocyte growth factor in rats experimentally envenomated with Bothrops jararaca venom: role of snake venom metalloproteasespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1016/j.toxicon.2019.03.003pt_BR
dc.identifier.urlhttp://dx.doi.org/10.1016/j.toxicon.2019.03.003pt_BR
dc.identifier.citationvolume162pt_BR
dc.subject.keywordBothrops jararaca snake venompt_BR
dc.subject.keywordHepatocyte growth factor activatorpt_BR
dc.subject.keywordHepatocyte growth factorpt_BR
dc.subject.keywordVenom-induced consumption coagulopathypt_BR
dc.subject.keywordSnake venom metalloproteasespt_BR
dc.subject.keywordSnake venom serine proteinasespt_BR
dc.relation.ispartofabbreviatedToxiconpt_BR
dc.identifier.citationabntv. 162, p. 9-14, abr. 2019pt_BR
dc.identifier.citationvancouver2019 Apr;162:9-14pt_BR
dc.contributor.butantanPrezoto, Benedito Carlos|:Pesquisador|:Lab. Farmacologia|:PrimeiroAutor:Autor de correspondênciapt_BR
dc.contributor.butantanGonçalves, Luis Roberto de Camargo|:Pesquisador:Docente Colaborador PPGTOX|:Lab. Fisiopatologia|:pt_BR
dc.contributor.butantanSampaio, Sandra Coccuzzo|:Pesquisador:Docente Permanente PPGTOX|:Lab. Fisiopatologia|:pt_BR
dc.contributor.butantanKato, Ellen Emi|:Aluno PPGTOX|:Lab. Fisiopatologia|:pt_BR
dc.contributor.butantanSano-Martins, Ida Sigueko|:Pesquisador|:Lab. Fisiopatologia|:pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2016/00211-0pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.subject.researchlineEnvenenamento e Terapêuticapt_BR
dc.description.dbindexedYespt_BR
item.grantfulltextembargo_29990101-
item.languageiso639-1English-
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item.openairetypeArticle-
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