New insights into the Hypotensins from Tityus serrulatus venom: pro-inflammatory and vasopeptidases modulation activities

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dc.contributor(LEFB) Lab. Estrutura e Função Biomoléculaspt_BR
dc.contributor(LBI) Lab. Imunoquímicapt_BR
dc.contributor.authorDuzzi, Brunopt_BR
dc.contributor.authorSilva, Cristiane Castilho Fernandes dapt_BR
dc.contributor.authorKodama, Roberto Tadashipt_BR
dc.contributor.authorCajado-Carvalho, Danielapt_BR
dc.contributor.authorSquaiella-Baptistão, Carla Cristinapt_BR
dc.contributor.authorPortaro, Fernanda Calheta Vieirapt_BR
dc.date.accessioned2021-12-22T18:56:21Z-
dc.date.available2021-12-22T18:56:21Z-
dc.date.issued2021pt_BR
dc.identifier.citationDuzzi B, Silva CCF, Kodama RT, Cajado-Carvalho D, Squaiella-Baptistão CC, Portaro FCV. New insights into the Hypotensins from Tityus serrulatus venom: pro-inflammatory and vasopeptidases modulation activities. Toxins. 2021 Nov;13(12):846. doi:10.3390/toxins13120846.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/4050-
dc.description.abstractThe Tityus serrulatus scorpion is considered the most dangerous of the Brazilian fauna due to the severe clinical manifestations in injured victims. Despite being abundant components of the venom, few linear peptides have been characterized so far, such as hypotensins. In vivo studies have demonstrated that hypotensin I (TsHpt-I) exerts hypotensive activity, with an angiotensin-converting enzyme (ACE)-independent mechanism of action. Since experiments have not yet been carried out to analyze the direct interaction of hypotensins with ACE, and to deepen the knowledge about these peptides, hypotensins I and II (TsHpt-II) were studied regarding their modulatory action over the activities of ACE and neprilysin (NEP), which are the peptidases involved in blood pressure control. Aiming to search for indications of possible pro-inflammatory action, hypotensins were also analyzed for their role in murine macrophage viability, the release of interleukins and phagocytic activity. TsHpt-I and -II were used in kinetic studies with the metallopeptidases ACE and NEP, and both hypotensins were able to increase the activity of ACE. TsHpt-I presented itself as an inhibitor of NEP, whereas TsHpt-II showed weak inhibition of the enzyme. The mechanism of inhibition of TsHpt-I in relation to NEP was defined as non-competitive, with an inhibition constant (Ki) of 4.35 μM. Concerning the analysis of cell viability and modulation of interleukin levels and phagocytic activity, BALB/c mice’s naïve macrophages were used, and an increase in TNF production in the presence of TsHpt-I and -II was observed, as well as an increase in IL-6 production in the presence of TsHpt-II only. Both hypotensins were able to increase the phagocytic activity of murine macrophages in vitro. The difference between TsHpt-I and -II is the residue at position 15, with a glutamine in TsHpt-I and a glutamic acid in TsHpt-II. Despite this, kinetic analyzes and cell assays indicated different actions of TsHpt-I and -II. Taken together, these results suggest a new mechanism for the hypotensive effects of TsHpt-I and -II. Furthermore, the release of some interleukins also suggests a role for these peptides in the venom inflammatory response. Even though these molecules have been well studied, the present results suggest a new mechanism for the hypotensive effects of TsHpt-Ipt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.extent846pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofToxinspt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleNew insights into the Hypotensins from Tityus serrulatus venom: pro-inflammatory and vasopeptidases modulation activitiespt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.3390/toxins13120846pt_BR
dc.identifier.urlhttps://doi.org/10.3390/toxins13120846pt_BR
dc.identifier.citationvolume13pt_BR
dc.identifier.citationissue12pt_BR
dc.subject.keywordTityus serrulatuspt_BR
dc.subject.keywordvenom componentspt_BR
dc.subject.keywordhypotensinspt_BR
dc.subject.keywordNEP inhibitionpt_BR
dc.subject.keywordcytokinespt_BR
dc.relation.ispartofabbreviatedToxinspt_BR
dc.identifier.citationabntv. 13, n. 12, 846, nov. 2021pt_BR
dc.identifier.citationvancouver2021 Nov;13(12):846pt_BR
dc.contributor.butantanDuzzi, Bruno|:Desvinculado|:Lab. de Estrutura e Função Biomoléculaspt_BR
dc.contributor.butantanSilva, Cristiane Castilho Fernandes da|:Desvinculado|:Lab. de Estrutura e Função Biomoléculaspt_BR
dc.contributor.butantanKodama, Roberto Tadashi|:Desvinculado|:Lab. de Estrutura e Função Biomoléculaspt_BR
dc.contributor.butantanCajado-Carvalho, Daniela|:Técnico|:Lab. de Estrutura e Função Biomoléculaspt_BR
dc.contributor.butantanSquaiella-Baptistão, Carla Cristina|:Pesquisador|:Lab. Imunoquímicapt_BR
dc.contributor.butantanPortaro, Fernanda Calheta Vieira|:Pesquisador:Docente permanente PPGTOX|:Lab. de Estrutura e Função Biomoléculaspt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2014/12976-5pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2013/15343-0pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2015/13124-5pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2019/20832-7pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦88882.377116/2019-01pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.languageiso639-1English-
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