5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways

Autores
Neuman, Isabel; Cooke, Mariana; Lemiña, Nicolás Agustín; Kazanietz, Marcelo Gabriel; Cornejo Maciel, Maria Fabiana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The OXE receptor is a GPCR activated by eicosanoids produced by the action of 5-lipoxygenase. We previously found that this membrane receptor participates in the regulation of cAMP-dependent and -independent steroidogenesis in human H295R adrenocortical carcinoma cells. In this study we analyzed the effects of the OXE receptor physiological activator 5-oxo-ETE on the growth and migration of H259R cells. While 5-oxo-ETE did not affect the growth of H295R cells, overexpression of OXE receptor caused an increase in cell proliferation, which was further increased by 5-oxo-ETE and blocked by 5-lipoxygenase inhibition. 5-oxo-ETE increased the migratory capacity of H295R cells in wound healing assays, but it did not induce the production of metalloproteases MMP-1, MMP-2, MMP-9 and MMP-10. The pro-migratory effect of 5-oxo-ETE was reduced by pharmacological inhibition of the MEK/ERK1/2, p38 and PKC pathways. 5-oxo-ETE caused significant activation of ERK and p38. ERK activation by the eicosanoid was reduced by the “pan” PKC inhibitor GF109203X but not by the classical PKC inhibitor Gö6976, suggesting the involvement of novel PKCs in this effect. Although H295R cells display detectable phosphorylation of Ser299 in PKCδ, a readout for the activation of this novel PKC, treatment with 5-oxo-ETE per se was unable to induce additional PKCδ activation. Our results revealed signaling effectors activated by 5-oxo-ETE in H295R cells and may have significant implications for our understanding of OXE receptor in adrenocortical cell pathophysiology.
Fil: Neuman, Isabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cooke, Mariana. University of Pennsylvania; Estados Unidos
Fil: Lemiña, Nicolás Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Fil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
5-OXO-EICOSATETRAENOIC ACID
ERK1/2
H295R HUMAN ADRENOCORTICAL CELLS
MIGRATION
OXOEICOSANOID RECEPTOR OXE-R
PKC
PROLIFERATION
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:11336/100901
Acceder
id CONICETDig_fe9ee7d8b216217a5fa390140421dba4
oai_identifier_str oai:ri.conicet.gov.ar:11336/100901
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathwaysNeuman, IsabelCooke, MarianaLemiña, Nicolás AgustínKazanietz, Marcelo GabrielCornejo Maciel, Maria Fabiana5-OXO-EICOSATETRAENOIC ACIDERK1/2H295R HUMAN ADRENOCORTICAL CELLSMIGRATIONOXOEICOSANOID RECEPTOR OXE-RPKCPROLIFERATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The OXE receptor is a GPCR activated by eicosanoids produced by the action of 5-lipoxygenase. We previously found that this membrane receptor participates in the regulation of cAMP-dependent and -independent steroidogenesis in human H295R adrenocortical carcinoma cells. In this study we analyzed the effects of the OXE receptor physiological activator 5-oxo-ETE on the growth and migration of H259R cells. While 5-oxo-ETE did not affect the growth of H295R cells, overexpression of OXE receptor caused an increase in cell proliferation, which was further increased by 5-oxo-ETE and blocked by 5-lipoxygenase inhibition. 5-oxo-ETE increased the migratory capacity of H295R cells in wound healing assays, but it did not induce the production of metalloproteases MMP-1, MMP-2, MMP-9 and MMP-10. The pro-migratory effect of 5-oxo-ETE was reduced by pharmacological inhibition of the MEK/ERK1/2, p38 and PKC pathways. 5-oxo-ETE caused significant activation of ERK and p38. ERK activation by the eicosanoid was reduced by the “pan” PKC inhibitor GF109203X but not by the classical PKC inhibitor Gö6976, suggesting the involvement of novel PKCs in this effect. Although H295R cells display detectable phosphorylation of Ser299 in PKCδ, a readout for the activation of this novel PKC, treatment with 5-oxo-ETE per se was unable to induce additional PKCδ activation. Our results revealed signaling effectors activated by 5-oxo-ETE in H295R cells and may have significant implications for our understanding of OXE receptor in adrenocortical cell pathophysiology.Fil: Neuman, Isabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cooke, Mariana. University of Pennsylvania; Estados UnidosFil: Lemiña, Nicolás Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosFil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaElsevier Science Inc2019-10info: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/11336/100901Neuman, Isabel; Cooke, Mariana; Lemiña, Nicolás Agustín; Kazanietz, Marcelo Gabriel; Cornejo Maciel, Maria Fabiana; 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways; Elsevier Science Inc; Prostaglandins; 144; 106346; 10-2019; 1-81098-88231098-8823CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.prostaglandins.2019.106346info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1098882319300292info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:16Zoai:ri.conicet.gov.ar:11336/100901instacron: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 13:00:16.602CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
title 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
spellingShingle 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
Neuman, Isabel
5-OXO-EICOSATETRAENOIC ACID
ERK1/2
H295R HUMAN ADRENOCORTICAL CELLS
MIGRATION
OXOEICOSANOID RECEPTOR OXE-R
PKC
PROLIFERATION
title_short 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
title_full 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
title_fullStr 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
title_full_unstemmed 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
title_sort 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways
dc.creator.none.fl_str_mv Neuman, Isabel
Cooke, Mariana
Lemiña, Nicolás Agustín
Kazanietz, Marcelo Gabriel
Cornejo Maciel, Maria Fabiana
author Neuman, Isabel
author_facet Neuman, Isabel
Cooke, Mariana
Lemiña, Nicolás Agustín
Kazanietz, Marcelo Gabriel
Cornejo Maciel, Maria Fabiana
author_role author
author2 Cooke, Mariana
Lemiña, Nicolás Agustín
Kazanietz, Marcelo Gabriel
Cornejo Maciel, Maria Fabiana
author2_role author
author
author
author
dc.subject.none.fl_str_mv 5-OXO-EICOSATETRAENOIC ACID
ERK1/2
H295R HUMAN ADRENOCORTICAL CELLS
MIGRATION
OXOEICOSANOID RECEPTOR OXE-R
PKC
PROLIFERATION
topic 5-OXO-EICOSATETRAENOIC ACID
ERK1/2
H295R HUMAN ADRENOCORTICAL CELLS
MIGRATION
OXOEICOSANOID RECEPTOR OXE-R
PKC
PROLIFERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The OXE receptor is a GPCR activated by eicosanoids produced by the action of 5-lipoxygenase. We previously found that this membrane receptor participates in the regulation of cAMP-dependent and -independent steroidogenesis in human H295R adrenocortical carcinoma cells. In this study we analyzed the effects of the OXE receptor physiological activator 5-oxo-ETE on the growth and migration of H259R cells. While 5-oxo-ETE did not affect the growth of H295R cells, overexpression of OXE receptor caused an increase in cell proliferation, which was further increased by 5-oxo-ETE and blocked by 5-lipoxygenase inhibition. 5-oxo-ETE increased the migratory capacity of H295R cells in wound healing assays, but it did not induce the production of metalloproteases MMP-1, MMP-2, MMP-9 and MMP-10. The pro-migratory effect of 5-oxo-ETE was reduced by pharmacological inhibition of the MEK/ERK1/2, p38 and PKC pathways. 5-oxo-ETE caused significant activation of ERK and p38. ERK activation by the eicosanoid was reduced by the “pan” PKC inhibitor GF109203X but not by the classical PKC inhibitor Gö6976, suggesting the involvement of novel PKCs in this effect. Although H295R cells display detectable phosphorylation of Ser299 in PKCδ, a readout for the activation of this novel PKC, treatment with 5-oxo-ETE per se was unable to induce additional PKCδ activation. Our results revealed signaling effectors activated by 5-oxo-ETE in H295R cells and may have significant implications for our understanding of OXE receptor in adrenocortical cell pathophysiology.
Fil: Neuman, Isabel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cooke, Mariana. University of Pennsylvania; Estados Unidos
Fil: Lemiña, Nicolás Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados Unidos
Fil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description The OXE receptor is a GPCR activated by eicosanoids produced by the action of 5-lipoxygenase. We previously found that this membrane receptor participates in the regulation of cAMP-dependent and -independent steroidogenesis in human H295R adrenocortical carcinoma cells. In this study we analyzed the effects of the OXE receptor physiological activator 5-oxo-ETE on the growth and migration of H259R cells. While 5-oxo-ETE did not affect the growth of H295R cells, overexpression of OXE receptor caused an increase in cell proliferation, which was further increased by 5-oxo-ETE and blocked by 5-lipoxygenase inhibition. 5-oxo-ETE increased the migratory capacity of H295R cells in wound healing assays, but it did not induce the production of metalloproteases MMP-1, MMP-2, MMP-9 and MMP-10. The pro-migratory effect of 5-oxo-ETE was reduced by pharmacological inhibition of the MEK/ERK1/2, p38 and PKC pathways. 5-oxo-ETE caused significant activation of ERK and p38. ERK activation by the eicosanoid was reduced by the “pan” PKC inhibitor GF109203X but not by the classical PKC inhibitor Gö6976, suggesting the involvement of novel PKCs in this effect. Although H295R cells display detectable phosphorylation of Ser299 in PKCδ, a readout for the activation of this novel PKC, treatment with 5-oxo-ETE per se was unable to induce additional PKCδ activation. Our results revealed signaling effectors activated by 5-oxo-ETE in H295R cells and may have significant implications for our understanding of OXE receptor in adrenocortical cell pathophysiology.
publishDate 2019
dc.date.none.fl_str_mv 2019-10
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/11336/100901
Neuman, Isabel; Cooke, Mariana; Lemiña, Nicolás Agustín; Kazanietz, Marcelo Gabriel; Cornejo Maciel, Maria Fabiana; 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways; Elsevier Science Inc; Prostaglandins; 144; 106346; 10-2019; 1-8
1098-8823
1098-8823
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100901
identifier_str_mv Neuman, Isabel; Cooke, Mariana; Lemiña, Nicolás Agustín; Kazanietz, Marcelo Gabriel; Cornejo Maciel, Maria Fabiana; 5-oxo-ETE activates migration of H295R adrenocortical cells via MAPK and PKC pathways; Elsevier Science Inc; Prostaglandins; 144; 106346; 10-2019; 1-8
1098-8823
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.prostaglandins.2019.106346
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1098882319300292
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
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
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 12.48226

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