Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)

8 páginas, 4 figuras, 1 tabla

Detalhes bibliográficos
Autores: Conlon, J. Michael, Attoub, Samir, Musale, Vishal, Leprince, Jérôme, Casewell, Nicholas R., Sanz, Libia, Calvete, Juan J.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/215201
Acesso em linha:http://hdl.handle.net/10261/215201
Access Level:acceso abierto
Palavra-chave:Cytotoxicity
Insulinotropic activity
Naja
Phospholipase A2
Three-finger toxins
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spelling Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)Conlon, J. MichaelAttoub, SamirMusale, VishalLeprince, JérômeCasewell, Nicholas R.Sanz, LibiaCalvete, Juan J.CytotoxicityInsulinotropic activityNajaPhospholipase A2Three-finger toxins8 páginas, 4 figuras, 1 tablaFour peptides with cytotoxic activity against BRIN-BD11 rat clonal β-cells were purified from the venom of the black-necked spitting cobra Naja nigricollis using reversed-phase HPLC. The peptides were identified as members of the three-finger superfamily of snake toxins by ESI-MS/MS sequencing of tryptic peptides. The most potent peptide (cytotoxin-1N) showed strong cytotoxic activity against three human tumor-derived cell lines (LC50 = 0.8 ± 0.2 μM for A549 non-small cell lung adenocarcinoma cells; LC50 = 7 ± 1 μM for MDA-MB-231 breast adenocarcinoma cells; and LC50 = 9 ± 1 μM for HT-29 colorectal adenocarcinoma cells). However, all the peptides were to varying degrees cytotoxic against HUVEC human umbilical vein endothelial cells (LC50 in the range 2-22 μM) and cytotoxin-2N was moderately hemolytic (LC50 = 45 ± 3 μM against mouse erythrocytes). The lack of differential activity against cells derived from non-neoplastic tissue limits their potential for development into anti-cancer agents. In addition, two proteins in the venom, identified as isoforms of phospholipase A2, effectively stimulated insulin release from BRIN-BD11 cells (an approximately 6-fold increase in rate compared with 5.6 mM glucose alone) at a concentration (1 μM) that was not cytotoxic to the cells suggesting possible application in therapy for Type 2 diabetes.This work was partly supported by the Ministerio de Ciencia, Innovacion � y Universidades, Madrid, Spain (grant number BFU 2017- 89103-P) to JJC.Peer reviewedElsevierMinisterio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/215201reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-89103-Phttp://dx.doi.org/10.1016/j.toxcx.2020.100030Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2152012026-05-22T06:33:51Z
dc.title.none.fl_str_mv Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
title Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
spellingShingle Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
Conlon, J. Michael
Cytotoxicity
Insulinotropic activity
Naja
Phospholipase A2
Three-finger toxins
title_short Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
title_full Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
title_fullStr Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
title_full_unstemmed Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
title_sort Isolation and characterization of cytotoxic and insulin-releasing components from the venom of the black-necked spitting cobra Naja nigricollis (Elapidae)
dc.creator.none.fl_str_mv Conlon, J. Michael
Attoub, Samir
Musale, Vishal
Leprince, Jérôme
Casewell, Nicholas R.
Sanz, Libia
Calvete, Juan J.
author Conlon, J. Michael
author_facet Conlon, J. Michael
Attoub, Samir
Musale, Vishal
Leprince, Jérôme
Casewell, Nicholas R.
Sanz, Libia
Calvete, Juan J.
author_role author
author2 Attoub, Samir
Musale, Vishal
Leprince, Jérôme
Casewell, Nicholas R.
Sanz, Libia
Calvete, Juan J.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cytotoxicity
Insulinotropic activity
Naja
Phospholipase A2
Three-finger toxins
topic Cytotoxicity
Insulinotropic activity
Naja
Phospholipase A2
Three-finger toxins
description 8 páginas, 4 figuras, 1 tabla
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/215201
url http://hdl.handle.net/10261/215201
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017-89103-P
http://dx.doi.org/10.1016/j.toxcx.2020.100030

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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