A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes

Autores
Lamas Bervejillo, M.; Bonanata, Julieta; Franchini, Gisela Raquel; Richeri, A.; Marqués, J.M.; Freeman, B.A.; Schopfer, Francisco Jose; Coitiño, E.L.; Córsico, Betina; Rubbo, H.; Ferreira, A.M.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nitro-fatty acids (NO2-FA) are electrophilic lipid mediators derived from unsaturated fatty acid nitration. These species are produced endogenously by metabolic and inflammatory reactions and mediate anti-oxidative and anti-inflammatory responses. NO2-FA have been postulated as partial agonists of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ), which is predominantly expressed in adipocytes and myeloid cells. Herein, we explored molecular and cellular events associated with PPARγ activation by NO2-FA in monocytes and macrophages. NO2-FA induced the expression of two PPARγ reporter genes, Fatty Acid Binding Protein 4 (FABP4) and the scavenger receptor CD36, at early stages of monocyte differentiation into macrophages. These responses were inhibited by the specific PPARγ inhibitor GW9662. Attenuated NO2-FA effects on PPARγ signaling were observed once cells were differentiated into macrophages, with a significant but lower FABP4 upregulation, and no induction of CD36. Using in vitro and in silico approaches, we demonstrated that NO2-FA bind to FABP4. Furthermore, the inhibition of monocyte FA binding by FABP4 diminished NO2-FA-induced upregulation of reporter genes that are transcriptionally regulated by PPARγ, Keap1/Nrf2 and HSF1, indicating that FABP4 inhibition mitigates NO2-FA signaling actions. Overall, our results affirm that NO2-FA activate PPARγ in monocytes and upregulate FABP4 expression, thus promoting a positive amplification loop for the downstream signaling actions of this mediator.
Fil: Lamas Bervejillo, M.. Universidad de la República; Uruguay
Fil: Bonanata, Julieta. Universidad de la República; Uruguay
Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Richeri, A.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Marqués, J.M.. Universidad de la República; Uruguay
Fil: Freeman, B.A.. University of Pittsburgh; Estados Unidos
Fil: Schopfer, Francisco Jose. University of Pittsburgh; Estados Unidos
Fil: Coitiño, E.L.. Universidad de la República; Uruguay
Fil: Córsico, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Rubbo, H.. Universidad de la República; Uruguay
Fil: Ferreira, A.M.. Universidad de la República; Uruguay
Materia
FATTY ACID BINDING PROTEIN 4
LIPID SIGNALING
MACROPHAGES
MONOCYTES
NITRO-FATTY ACIDS
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/143638
Acceder
id CONICETDig_4e6783172a8bb7061baf819a148afe93
oai_identifier_str oai:ri.conicet.gov.ar:11336/143638
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenesLamas Bervejillo, M.Bonanata, JulietaFranchini, Gisela RaquelRicheri, A.Marqués, J.M.Freeman, B.A.Schopfer, Francisco JoseCoitiño, E.L.Córsico, BetinaRubbo, H.Ferreira, A.M.FATTY ACID BINDING PROTEIN 4LIPID SIGNALINGMACROPHAGESMONOCYTESNITRO-FATTY ACIDSPEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMAhttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1Nitro-fatty acids (NO2-FA) are electrophilic lipid mediators derived from unsaturated fatty acid nitration. These species are produced endogenously by metabolic and inflammatory reactions and mediate anti-oxidative and anti-inflammatory responses. NO2-FA have been postulated as partial agonists of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ), which is predominantly expressed in adipocytes and myeloid cells. Herein, we explored molecular and cellular events associated with PPARγ activation by NO2-FA in monocytes and macrophages. NO2-FA induced the expression of two PPARγ reporter genes, Fatty Acid Binding Protein 4 (FABP4) and the scavenger receptor CD36, at early stages of monocyte differentiation into macrophages. These responses were inhibited by the specific PPARγ inhibitor GW9662. Attenuated NO2-FA effects on PPARγ signaling were observed once cells were differentiated into macrophages, with a significant but lower FABP4 upregulation, and no induction of CD36. Using in vitro and in silico approaches, we demonstrated that NO2-FA bind to FABP4. Furthermore, the inhibition of monocyte FA binding by FABP4 diminished NO2-FA-induced upregulation of reporter genes that are transcriptionally regulated by PPARγ, Keap1/Nrf2 and HSF1, indicating that FABP4 inhibition mitigates NO2-FA signaling actions. Overall, our results affirm that NO2-FA activate PPARγ in monocytes and upregulate FABP4 expression, thus promoting a positive amplification loop for the downstream signaling actions of this mediator.Fil: Lamas Bervejillo, M.. Universidad de la República; UruguayFil: Bonanata, Julieta. Universidad de la República; UruguayFil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Richeri, A.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Marqués, J.M.. Universidad de la República; UruguayFil: Freeman, B.A.. University of Pittsburgh; Estados UnidosFil: Schopfer, Francisco Jose. University of Pittsburgh; Estados UnidosFil: Coitiño, E.L.. Universidad de la República; UruguayFil: Córsico, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Rubbo, H.. Universidad de la República; UruguayFil: Ferreira, A.M.. Universidad de la República; UruguayElsevier Science2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/143638Lamas Bervejillo, M.; Bonanata, Julieta; Franchini, Gisela Raquel; Richeri, A.; Marqués, J.M.; et al.; A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes; Elsevier Science; Redox Biology; 29; 1-2020; 1-152213-2317CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.redox.2019.101376info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231719308523info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:37:38Zoai:ri.conicet.gov.ar:11336/143638instacron: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:34982025-10-15 14:37:38.567CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
title A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
spellingShingle A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
Lamas Bervejillo, M.
FATTY ACID BINDING PROTEIN 4
LIPID SIGNALING
MACROPHAGES
MONOCYTES
NITRO-FATTY ACIDS
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA
title_short A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
title_full A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
title_fullStr A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
title_full_unstemmed A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
title_sort A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes
dc.creator.none.fl_str_mv Lamas Bervejillo, M.
Bonanata, Julieta
Franchini, Gisela Raquel
Richeri, A.
Marqués, J.M.
Freeman, B.A.
Schopfer, Francisco Jose
Coitiño, E.L.
Córsico, Betina
Rubbo, H.
Ferreira, A.M.
author Lamas Bervejillo, M.
author_facet Lamas Bervejillo, M.
Bonanata, Julieta
Franchini, Gisela Raquel
Richeri, A.
Marqués, J.M.
Freeman, B.A.
Schopfer, Francisco Jose
Coitiño, E.L.
Córsico, Betina
Rubbo, H.
Ferreira, A.M.
author_role author
author2 Bonanata, Julieta
Franchini, Gisela Raquel
Richeri, A.
Marqués, J.M.
Freeman, B.A.
Schopfer, Francisco Jose
Coitiño, E.L.
Córsico, Betina
Rubbo, H.
Ferreira, A.M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FATTY ACID BINDING PROTEIN 4
LIPID SIGNALING
MACROPHAGES
MONOCYTES
NITRO-FATTY ACIDS
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA
topic FATTY ACID BINDING PROTEIN 4
LIPID SIGNALING
MACROPHAGES
MONOCYTES
NITRO-FATTY ACIDS
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.7
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nitro-fatty acids (NO2-FA) are electrophilic lipid mediators derived from unsaturated fatty acid nitration. These species are produced endogenously by metabolic and inflammatory reactions and mediate anti-oxidative and anti-inflammatory responses. NO2-FA have been postulated as partial agonists of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ), which is predominantly expressed in adipocytes and myeloid cells. Herein, we explored molecular and cellular events associated with PPARγ activation by NO2-FA in monocytes and macrophages. NO2-FA induced the expression of two PPARγ reporter genes, Fatty Acid Binding Protein 4 (FABP4) and the scavenger receptor CD36, at early stages of monocyte differentiation into macrophages. These responses were inhibited by the specific PPARγ inhibitor GW9662. Attenuated NO2-FA effects on PPARγ signaling were observed once cells were differentiated into macrophages, with a significant but lower FABP4 upregulation, and no induction of CD36. Using in vitro and in silico approaches, we demonstrated that NO2-FA bind to FABP4. Furthermore, the inhibition of monocyte FA binding by FABP4 diminished NO2-FA-induced upregulation of reporter genes that are transcriptionally regulated by PPARγ, Keap1/Nrf2 and HSF1, indicating that FABP4 inhibition mitigates NO2-FA signaling actions. Overall, our results affirm that NO2-FA activate PPARγ in monocytes and upregulate FABP4 expression, thus promoting a positive amplification loop for the downstream signaling actions of this mediator.
Fil: Lamas Bervejillo, M.. Universidad de la República; Uruguay
Fil: Bonanata, Julieta. Universidad de la República; Uruguay
Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Richeri, A.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Marqués, J.M.. Universidad de la República; Uruguay
Fil: Freeman, B.A.. University of Pittsburgh; Estados Unidos
Fil: Schopfer, Francisco Jose. University of Pittsburgh; Estados Unidos
Fil: Coitiño, E.L.. Universidad de la República; Uruguay
Fil: Córsico, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Rubbo, H.. Universidad de la República; Uruguay
Fil: Ferreira, A.M.. Universidad de la República; Uruguay
description Nitro-fatty acids (NO2-FA) are electrophilic lipid mediators derived from unsaturated fatty acid nitration. These species are produced endogenously by metabolic and inflammatory reactions and mediate anti-oxidative and anti-inflammatory responses. NO2-FA have been postulated as partial agonists of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ), which is predominantly expressed in adipocytes and myeloid cells. Herein, we explored molecular and cellular events associated with PPARγ activation by NO2-FA in monocytes and macrophages. NO2-FA induced the expression of two PPARγ reporter genes, Fatty Acid Binding Protein 4 (FABP4) and the scavenger receptor CD36, at early stages of monocyte differentiation into macrophages. These responses were inhibited by the specific PPARγ inhibitor GW9662. Attenuated NO2-FA effects on PPARγ signaling were observed once cells were differentiated into macrophages, with a significant but lower FABP4 upregulation, and no induction of CD36. Using in vitro and in silico approaches, we demonstrated that NO2-FA bind to FABP4. Furthermore, the inhibition of monocyte FA binding by FABP4 diminished NO2-FA-induced upregulation of reporter genes that are transcriptionally regulated by PPARγ, Keap1/Nrf2 and HSF1, indicating that FABP4 inhibition mitigates NO2-FA signaling actions. Overall, our results affirm that NO2-FA activate PPARγ in monocytes and upregulate FABP4 expression, thus promoting a positive amplification loop for the downstream signaling actions of this mediator.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
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/11336/143638
Lamas Bervejillo, M.; Bonanata, Julieta; Franchini, Gisela Raquel; Richeri, A.; Marqués, J.M.; et al.; A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes; Elsevier Science; Redox Biology; 29; 1-2020; 1-15
2213-2317
CONICET Digital
CONICET
url http://hdl.handle.net/11336/143638
identifier_str_mv Lamas Bervejillo, M.; Bonanata, Julieta; Franchini, Gisela Raquel; Richeri, A.; Marqués, J.M.; et al.; A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes; Elsevier Science; Redox Biology; 29; 1-2020; 1-15
2213-2317
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.redox.2019.101376
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231719308523
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 13.22299

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