Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis

Autores
Bustillo, Soledad; Garcia Denegri, María Emilia; Gay, Claudia Carolina; Van de Velde, Andrea Carolina; Acosta, Ofelia Cristina; Angulo, Yamileth; Lomonte, Bruno; Gutierrez, José María; Leiva, Laura Cristina Ana
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Microvessel disruption leading to hemorrhage stands among the most dangerous consequences of envenomings by snakes of the family Viperidae. A PIII metalloproteinase (SVMP), balteragin, purified from the venom of the snake Bothrops alternatus, displays a potent hemorrhagic effect, and a moderate myotoxicity in vivo. Previous studies described the ability of this SVMP to induce the detachment of C2C12 myoblasts in culture, without causing cytolysis. Surprisingly, a purified acidic phospholipase A2 (PLA2) from the same venom was found to increase this detaching activity of the SVMP on myoblasts. Since endothelial cells are a natural target of SVMPs in vivo, the possibility that this synergistic effect is also observed on this cell type was explored in the present work. In addition, a first approach of the mechanism of action of this effect was studied. Results clearly confirm that the acidic PLA2, despite lacking toxicity towards endothelial cells, significantly enhances the detaching effect of the SVMP even at a concentration as low as 1 μg/mL. Inhibition of enzymatic activity of the PLA2 by chemical modification with p-bromophenacyl bromide did not affect the synergistic activity, suggesting that this effect is not dependent on phospholipase enzymatic activity and may instead be the consequence of an interaction of the PLA2 with endothelial cell plasma membrane. To our knowledge, this is the first report of a synergistic action of a non toxic PLA2 in enhancing the detachment of endothelial cells induced by a metalloproteinase.
Fil: Bustillo, Soledad. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Garcia Denegri, María Emilia. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gay, Claudia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Van de Velde, Andrea Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Acosta, Ofelia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina
Fil: Angulo, Yamileth. Universidad de Costa Rica; Costa Rica
Fil: Lomonte, Bruno. Universidad de Costa Rica; Costa Rica
Fil: Gutierrez, José María. Universidad de Costa Rica; Costa Rica
Fil: Leiva, Laura Cristina Ana. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Materia
Endothelial Cells
Metalloproteinase
Phospholipase A2
Snake Venoms
Synergism
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38051
Acceder
id CONICETDig_e5d739c7fdf9947656af31df8984b0e7
oai_identifier_str oai:ri.conicet.gov.ar:11336/38051
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysisBustillo, SoledadGarcia Denegri, María EmiliaGay, Claudia CarolinaVan de Velde, Andrea CarolinaAcosta, Ofelia CristinaAngulo, YamilethLomonte, BrunoGutierrez, José MaríaLeiva, Laura Cristina AnaEndothelial CellsMetalloproteinasePhospholipase A2Snake VenomsSynergismhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Microvessel disruption leading to hemorrhage stands among the most dangerous consequences of envenomings by snakes of the family Viperidae. A PIII metalloproteinase (SVMP), balteragin, purified from the venom of the snake Bothrops alternatus, displays a potent hemorrhagic effect, and a moderate myotoxicity in vivo. Previous studies described the ability of this SVMP to induce the detachment of C2C12 myoblasts in culture, without causing cytolysis. Surprisingly, a purified acidic phospholipase A2 (PLA2) from the same venom was found to increase this detaching activity of the SVMP on myoblasts. Since endothelial cells are a natural target of SVMPs in vivo, the possibility that this synergistic effect is also observed on this cell type was explored in the present work. In addition, a first approach of the mechanism of action of this effect was studied. Results clearly confirm that the acidic PLA2, despite lacking toxicity towards endothelial cells, significantly enhances the detaching effect of the SVMP even at a concentration as low as 1 μg/mL. Inhibition of enzymatic activity of the PLA2 by chemical modification with p-bromophenacyl bromide did not affect the synergistic activity, suggesting that this effect is not dependent on phospholipase enzymatic activity and may instead be the consequence of an interaction of the PLA2 with endothelial cell plasma membrane. To our knowledge, this is the first report of a synergistic action of a non toxic PLA2 in enhancing the detachment of endothelial cells induced by a metalloproteinase.Fil: Bustillo, Soledad. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; ArgentinaFil: Garcia Denegri, María Emilia. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gay, Claudia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; ArgentinaFil: Van de Velde, Andrea Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; ArgentinaFil: Acosta, Ofelia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; ArgentinaFil: Angulo, Yamileth. Universidad de Costa Rica; Costa RicaFil: Lomonte, Bruno. Universidad de Costa Rica; Costa RicaFil: Gutierrez, José María. Universidad de Costa Rica; Costa RicaFil: Leiva, Laura Cristina Ana. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; ArgentinaElsevier Ireland2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38051Bustillo, Soledad; Garcia Denegri, María Emilia; Gay, Claudia Carolina; Van de Velde, Andrea Carolina; Acosta, Ofelia Cristina; et al.; Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis; Elsevier Ireland; Chemico-biological Interactions; 240; 10-2015; 30-360009-27971872-7786CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0009279715300314info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cbi.2015.08.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:12:50Zoai:ri.conicet.gov.ar:11336/38051instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:12:50.757CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
title Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
spellingShingle Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
Bustillo, Soledad
Endothelial Cells
Metalloproteinase
Phospholipase A2
Snake Venoms
Synergism
title_short Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
title_full Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
title_fullStr Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
title_full_unstemmed Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
title_sort Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis
dc.creator.none.fl_str_mv Bustillo, Soledad
Garcia Denegri, María Emilia
Gay, Claudia Carolina
Van de Velde, Andrea Carolina
Acosta, Ofelia Cristina
Angulo, Yamileth
Lomonte, Bruno
Gutierrez, José María
Leiva, Laura Cristina Ana
author Bustillo, Soledad
author_facet Bustillo, Soledad
Garcia Denegri, María Emilia
Gay, Claudia Carolina
Van de Velde, Andrea Carolina
Acosta, Ofelia Cristina
Angulo, Yamileth
Lomonte, Bruno
Gutierrez, José María
Leiva, Laura Cristina Ana
author_role author
author2 Garcia Denegri, María Emilia
Gay, Claudia Carolina
Van de Velde, Andrea Carolina
Acosta, Ofelia Cristina
Angulo, Yamileth
Lomonte, Bruno
Gutierrez, José María
Leiva, Laura Cristina Ana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endothelial Cells
Metalloproteinase
Phospholipase A2
Snake Venoms
Synergism
topic Endothelial Cells
Metalloproteinase
Phospholipase A2
Snake Venoms
Synergism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Microvessel disruption leading to hemorrhage stands among the most dangerous consequences of envenomings by snakes of the family Viperidae. A PIII metalloproteinase (SVMP), balteragin, purified from the venom of the snake Bothrops alternatus, displays a potent hemorrhagic effect, and a moderate myotoxicity in vivo. Previous studies described the ability of this SVMP to induce the detachment of C2C12 myoblasts in culture, without causing cytolysis. Surprisingly, a purified acidic phospholipase A2 (PLA2) from the same venom was found to increase this detaching activity of the SVMP on myoblasts. Since endothelial cells are a natural target of SVMPs in vivo, the possibility that this synergistic effect is also observed on this cell type was explored in the present work. In addition, a first approach of the mechanism of action of this effect was studied. Results clearly confirm that the acidic PLA2, despite lacking toxicity towards endothelial cells, significantly enhances the detaching effect of the SVMP even at a concentration as low as 1 μg/mL. Inhibition of enzymatic activity of the PLA2 by chemical modification with p-bromophenacyl bromide did not affect the synergistic activity, suggesting that this effect is not dependent on phospholipase enzymatic activity and may instead be the consequence of an interaction of the PLA2 with endothelial cell plasma membrane. To our knowledge, this is the first report of a synergistic action of a non toxic PLA2 in enhancing the detachment of endothelial cells induced by a metalloproteinase.
Fil: Bustillo, Soledad. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Garcia Denegri, María Emilia. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gay, Claudia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Van de Velde, Andrea Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
Fil: Acosta, Ofelia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina
Fil: Angulo, Yamileth. Universidad de Costa Rica; Costa Rica
Fil: Lomonte, Bruno. Universidad de Costa Rica; Costa Rica
Fil: Gutierrez, José María. Universidad de Costa Rica; Costa Rica
Fil: Leiva, Laura Cristina Ana. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Bioquímica. Laboratorio de Investigación en Proteínas; Argentina
description Microvessel disruption leading to hemorrhage stands among the most dangerous consequences of envenomings by snakes of the family Viperidae. A PIII metalloproteinase (SVMP), balteragin, purified from the venom of the snake Bothrops alternatus, displays a potent hemorrhagic effect, and a moderate myotoxicity in vivo. Previous studies described the ability of this SVMP to induce the detachment of C2C12 myoblasts in culture, without causing cytolysis. Surprisingly, a purified acidic phospholipase A2 (PLA2) from the same venom was found to increase this detaching activity of the SVMP on myoblasts. Since endothelial cells are a natural target of SVMPs in vivo, the possibility that this synergistic effect is also observed on this cell type was explored in the present work. In addition, a first approach of the mechanism of action of this effect was studied. Results clearly confirm that the acidic PLA2, despite lacking toxicity towards endothelial cells, significantly enhances the detaching effect of the SVMP even at a concentration as low as 1 μg/mL. Inhibition of enzymatic activity of the PLA2 by chemical modification with p-bromophenacyl bromide did not affect the synergistic activity, suggesting that this effect is not dependent on phospholipase enzymatic activity and may instead be the consequence of an interaction of the PLA2 with endothelial cell plasma membrane. To our knowledge, this is the first report of a synergistic action of a non toxic PLA2 in enhancing the detachment of endothelial cells induced by a metalloproteinase.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38051
Bustillo, Soledad; Garcia Denegri, María Emilia; Gay, Claudia Carolina; Van de Velde, Andrea Carolina; Acosta, Ofelia Cristina; et al.; Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis; Elsevier Ireland; Chemico-biological Interactions; 240; 10-2015; 30-36
0009-2797
1872-7786
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38051
identifier_str_mv Bustillo, Soledad; Garcia Denegri, María Emilia; Gay, Claudia Carolina; Van de Velde, Andrea Carolina; Acosta, Ofelia Cristina; et al.; Phospholipase A2 enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis; Elsevier Ireland; Chemico-biological Interactions; 240; 10-2015; 30-36
0009-2797
1872-7786
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0009279715300314
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cbi.2015.08.002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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