Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macr...

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Autores: Arana Urbieta, Lide, Gangoiti Muñecas, Patricia, Ouro Villasante, Alberto, Rivera Líbano, Io Guané, Ordóñez Zaragoza, Marta, Trueba Conde, Miguel Ángel, Lankalapalli, Ravi S., Bittman, Robert, Gómez Muñoz, Antonio
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/65968
Acceso en línea:http://hdl.handle.net/10810/65968
Access Level:acceso abierto
Palabra clave:ceramides
ceramide 1-phosphate
NADPH oxidase
ROS
proliferation
sphingolipids
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spelling Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphateArana Urbieta, LideGangoiti Muñecas, PatriciaOuro Villasante, AlbertoRivera Líbano, Io GuanéOrdóñez Zaragoza, MartaTrueba Conde, Miguel ÁngelLankalapalli, Ravi S.Bittman, RobertGómez Muñoz, Antonioceramidesceramide 1-phosphateNADPH oxidaseROSproliferationsphingolipidsWe previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A2 and protein kinase C-, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC- and cPLA2- in this pathway.This work was supported by grants BFU2009-13314/BFI from Ministerio de Ciencia e Innovación (MICINN) (Madrid, Spain), IT-353-10 from Departamento de Educación, Universidades e Investigación del Gobierno Vasco (GV/EJ), SA-2010/00013 from Departamento de Industria, Comercio y Turismo del Gobierno Vasco (Basque Government, GV/EJ) to AGM, and grant HL083187 from the National Institutes of Health to RB. LA and AO are the recipients of fellowships from the Basque Government.Elsevier202420242011info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/65968reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/FU2009-13314/BFIhttps://www.sciencedirect.com/science/article/pii/S001448271100470info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/© 2011 Elsevier under CC BY-NC-ND licenseoai:addi.ehu.eus:10810/659682026-06-18T09:23:17Z
dc.title.none.fl_str_mv Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
title Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
spellingShingle Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
Arana Urbieta, Lide
ceramides
ceramide 1-phosphate
NADPH oxidase
ROS
proliferation
sphingolipids
title_short Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
title_full Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
title_fullStr Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
title_full_unstemmed Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
title_sort Generation of Reactive Oxygen Species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate
dc.creator.none.fl_str_mv Arana Urbieta, Lide
Gangoiti Muñecas, Patricia
Ouro Villasante, Alberto
Rivera Líbano, Io Guané
Ordóñez Zaragoza, Marta
Trueba Conde, Miguel Ángel
Lankalapalli, Ravi S.
Bittman, Robert
Gómez Muñoz, Antonio
author Arana Urbieta, Lide
author_facet Arana Urbieta, Lide
Gangoiti Muñecas, Patricia
Ouro Villasante, Alberto
Rivera Líbano, Io Guané
Ordóñez Zaragoza, Marta
Trueba Conde, Miguel Ángel
Lankalapalli, Ravi S.
Bittman, Robert
Gómez Muñoz, Antonio
author_role author
author2 Gangoiti Muñecas, Patricia
Ouro Villasante, Alberto
Rivera Líbano, Io Guané
Ordóñez Zaragoza, Marta
Trueba Conde, Miguel Ángel
Lankalapalli, Ravi S.
Bittman, Robert
Gómez Muñoz, Antonio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ceramides
ceramide 1-phosphate
NADPH oxidase
ROS
proliferation
sphingolipids
topic ceramides
ceramide 1-phosphate
NADPH oxidase
ROS
proliferation
sphingolipids
description We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A2 and protein kinase C-, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC- and cPLA2- in this pathway.
publishDate 2011
dc.date.none.fl_str_mv 2011
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/65968
url http://hdl.handle.net/10810/65968
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/FU2009-13314/BFI
https://www.sciencedirect.com/science/article/pii/S001448271100470
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
© 2011 Elsevier under CC BY-NC-ND license
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
© 2011 Elsevier under CC BY-NC-ND license
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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