New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom

Autores
Sasovsky, Daniela Jaqueline; Oliveira, Ana K.; Silva, Dilza Trevisan; Ojeda, Gonzalo Adrian; Almarza, Cristopher; Lomonte, Bruno; Fox, Jay W.; Urra, Félix A.; Bustillo, Soledad
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Phospholipases A2 (PLA2s) are key mediators of the cytotoxic and inflammatory activitiesof snake venoms. While PLA2 isoforms from Bothrops diporus venom have been characterizedand shown to possess antimetastatic and antiangiogenic properties, their impact onmitochondrial bioenergetics and immune modulation has not yet been investigated. In thisstudy, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA2susing integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231breast cancer cells, pooled PLA2s induced a dose-dependent decrease in MTT-reducingactivity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreasedNADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-timeimpedance measurements further revealed a marked inhibition of cell proliferation. Inhuman PBMCs, pooled PLA2s elicited a dynamic cytokine program, inducing early cytotoxic(Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by latepro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysisof a single purified PLA2 isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specificimmunomodulatory properties. Altogether, these findings provide the first integratedcharacterization of mitochondrial and immune perturbations induced by B. diporus PLA2s,expanding their recognized biological scope and underscoring their potential as moleculartemplates for novel pharmacological strategies targeting mitochondrial vulnerabilities ormodulating the tumor immune microenvironment.
Fil: Sasovsky, Daniela Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Oliveira, Ana K.. University of Virginia; Estados Unidos
Fil: Silva, Dilza Trevisan. University of Virginia; Estados Unidos
Fil: Ojeda, Gonzalo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Almarza, Cristopher. Universidad de Chile.; Chile
Fil: Lomonte, Bruno. Universidad de Costa Rica; Costa Rica
Fil: Fox, Jay W.. University of Virginia; Estados Unidos
Fil: Urra, Félix A.. Universidad de Chile.; Chile
Fil: Bustillo, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Materia
BOTHROPS DIPORUS
PHOSPHOLIPASES A2
MITOCHONDRIAL DYSFUNCTION
CYTOKINE MODULATION
IMMUNOMETABOLISM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/289711
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus VenomSasovsky, Daniela JaquelineOliveira, Ana K.Silva, Dilza TrevisanOjeda, Gonzalo AdrianAlmarza, CristopherLomonte, BrunoFox, Jay W.Urra, Félix A.Bustillo, SoledadBOTHROPS DIPORUSPHOSPHOLIPASES A2MITOCHONDRIAL DYSFUNCTIONCYTOKINE MODULATIONIMMUNOMETABOLISMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Phospholipases A2 (PLA2s) are key mediators of the cytotoxic and inflammatory activitiesof snake venoms. While PLA2 isoforms from Bothrops diporus venom have been characterizedand shown to possess antimetastatic and antiangiogenic properties, their impact onmitochondrial bioenergetics and immune modulation has not yet been investigated. In thisstudy, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA2susing integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231breast cancer cells, pooled PLA2s induced a dose-dependent decrease in MTT-reducingactivity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreasedNADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-timeimpedance measurements further revealed a marked inhibition of cell proliferation. Inhuman PBMCs, pooled PLA2s elicited a dynamic cytokine program, inducing early cytotoxic(Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by latepro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysisof a single purified PLA2 isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specificimmunomodulatory properties. Altogether, these findings provide the first integratedcharacterization of mitochondrial and immune perturbations induced by B. diporus PLA2s,expanding their recognized biological scope and underscoring their potential as moleculartemplates for novel pharmacological strategies targeting mitochondrial vulnerabilities ormodulating the tumor immune microenvironment.Fil: Sasovsky, Daniela Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Oliveira, Ana K.. University of Virginia; Estados UnidosFil: Silva, Dilza Trevisan. University of Virginia; Estados UnidosFil: Ojeda, Gonzalo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Almarza, Cristopher. Universidad de Chile.; ChileFil: Lomonte, Bruno. Universidad de Costa Rica; Costa RicaFil: Fox, Jay W.. University of Virginia; Estados UnidosFil: Urra, Félix A.. Universidad de Chile.; ChileFil: Bustillo, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaMDPI2026-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/289711Sasovsky, Daniela Jaqueline; Oliveira, Ana K.; Silva, Dilza Trevisan; Ojeda, Gonzalo Adrian; Almarza, Cristopher; et al.; New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom; MDPI; Toxins; 18; 2; 2-2026; 1-152072-6651CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/18/2/114info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins18020114info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:55:13Zoai:ri.conicet.gov.ar:11336/289711instacron: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:34982026-08-25 14:55:13.682CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
title New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
spellingShingle New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
Sasovsky, Daniela Jaqueline
BOTHROPS DIPORUS
PHOSPHOLIPASES A2
MITOCHONDRIAL DYSFUNCTION
CYTOKINE MODULATION
IMMUNOMETABOLISM
title_short New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
title_full New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
title_fullStr New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
title_full_unstemmed New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
title_sort New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom
dc.creator.none.fl_str_mv Sasovsky, Daniela Jaqueline
Oliveira, Ana K.
Silva, Dilza Trevisan
Ojeda, Gonzalo Adrian
Almarza, Cristopher
Lomonte, Bruno
Fox, Jay W.
Urra, Félix A.
Bustillo, Soledad
author Sasovsky, Daniela Jaqueline
author_facet Sasovsky, Daniela Jaqueline
Oliveira, Ana K.
Silva, Dilza Trevisan
Ojeda, Gonzalo Adrian
Almarza, Cristopher
Lomonte, Bruno
Fox, Jay W.
Urra, Félix A.
Bustillo, Soledad
author_role author
author2 Oliveira, Ana K.
Silva, Dilza Trevisan
Ojeda, Gonzalo Adrian
Almarza, Cristopher
Lomonte, Bruno
Fox, Jay W.
Urra, Félix A.
Bustillo, Soledad
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BOTHROPS DIPORUS
PHOSPHOLIPASES A2
MITOCHONDRIAL DYSFUNCTION
CYTOKINE MODULATION
IMMUNOMETABOLISM
topic BOTHROPS DIPORUS
PHOSPHOLIPASES A2
MITOCHONDRIAL DYSFUNCTION
CYTOKINE MODULATION
IMMUNOMETABOLISM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Phospholipases A2 (PLA2s) are key mediators of the cytotoxic and inflammatory activitiesof snake venoms. While PLA2 isoforms from Bothrops diporus venom have been characterizedand shown to possess antimetastatic and antiangiogenic properties, their impact onmitochondrial bioenergetics and immune modulation has not yet been investigated. In thisstudy, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA2susing integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231breast cancer cells, pooled PLA2s induced a dose-dependent decrease in MTT-reducingactivity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreasedNADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-timeimpedance measurements further revealed a marked inhibition of cell proliferation. Inhuman PBMCs, pooled PLA2s elicited a dynamic cytokine program, inducing early cytotoxic(Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by latepro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysisof a single purified PLA2 isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specificimmunomodulatory properties. Altogether, these findings provide the first integratedcharacterization of mitochondrial and immune perturbations induced by B. diporus PLA2s,expanding their recognized biological scope and underscoring their potential as moleculartemplates for novel pharmacological strategies targeting mitochondrial vulnerabilities ormodulating the tumor immune microenvironment.
Fil: Sasovsky, Daniela Jaqueline. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Oliveira, Ana K.. University of Virginia; Estados Unidos
Fil: Silva, Dilza Trevisan. University of Virginia; Estados Unidos
Fil: Ojeda, Gonzalo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Almarza, Cristopher. Universidad de Chile.; Chile
Fil: Lomonte, Bruno. Universidad de Costa Rica; Costa Rica
Fil: Fox, Jay W.. University of Virginia; Estados Unidos
Fil: Urra, Félix A.. Universidad de Chile.; Chile
Fil: Bustillo, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
description Phospholipases A2 (PLA2s) are key mediators of the cytotoxic and inflammatory activitiesof snake venoms. While PLA2 isoforms from Bothrops diporus venom have been characterizedand shown to possess antimetastatic and antiangiogenic properties, their impact onmitochondrial bioenergetics and immune modulation has not yet been investigated. In thisstudy, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA2susing integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231breast cancer cells, pooled PLA2s induced a dose-dependent decrease in MTT-reducingactivity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreasedNADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-timeimpedance measurements further revealed a marked inhibition of cell proliferation. Inhuman PBMCs, pooled PLA2s elicited a dynamic cytokine program, inducing early cytotoxic(Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by latepro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysisof a single purified PLA2 isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specificimmunomodulatory properties. Altogether, these findings provide the first integratedcharacterization of mitochondrial and immune perturbations induced by B. diporus PLA2s,expanding their recognized biological scope and underscoring their potential as moleculartemplates for novel pharmacological strategies targeting mitochondrial vulnerabilities ormodulating the tumor immune microenvironment.
publishDate 2026
dc.date.none.fl_str_mv 2026-02
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/11336/289711
Sasovsky, Daniela Jaqueline; Oliveira, Ana K.; Silva, Dilza Trevisan; Ojeda, Gonzalo Adrian; Almarza, Cristopher; et al.; New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom; MDPI; Toxins; 18; 2; 2-2026; 1-15
2072-6651
CONICET Digital
CONICET
url http://hdl.handle.net/11336/289711
identifier_str_mv Sasovsky, Daniela Jaqueline; Oliveira, Ana K.; Silva, Dilza Trevisan; Ojeda, Gonzalo Adrian; Almarza, Cristopher; et al.; New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A2 from Bothrops diporus Venom; MDPI; Toxins; 18; 2; 2-2026; 1-15
2072-6651
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.mdpi.com/2072-6651/18/2/114
info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins18020114
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 13.24418

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