Mechanisms involved in p53 downregulation by leptin in trophoblastic cells

Autores
Toro, Ayelen Rayen; Pérez Pérez, Antonio; Corrales Gutiérrez, Isabel; Sánchez Margalet, Víctor; Varone, Cecilia Laura
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leptin, a 16-kDa polypeptide hormone, is produced by the adipocyte and can also be synthesized by placenta. We previously demonstrated that leptin promotes proliferation and survival in placenta, in part mediated by the p53 pathway. In this work, we investigated the mechanisms involved in leptin down-regulation of p53 level. The human first trimester cytotrophoblastic Swan-71 cell line and human placental explants at term were used. In order to study the late phase of apoptosis, triggered by serum deprivation, experiments of DNA fragmentation were carried out. Exogenous leptin added to human placental explants, showed a decrease on DNA ladder formation and MAPK pathway is involved in this leptin effect. We also found that under serum deprivation condition, leptin decreases p53 levels and the inhibitory leptin effect is lost when cells were pretreated with 50 μM PD98059 or 10 μM LY29004; or were transfected with dominant negative mutants of intermediates of these pathways, suggesting that MAPK and PI3K signaling pathways are necessaries for leptin action. Additionally, leptin diminished Ser-46 p53 phosphorylation and this effect in placental explants was mediated by the activation of MAPK and PI3K pathways. Finally, in order to assess leptin effect on p53 half-life experiments with cycloheximide were performed and MDM-2 expression was analyzed. Leptin diminished p53 half-life and up-regulated MDM-2 expression. In summary, we provided evidence suggesting that leptin anti-apoptotic effect is mediated by MAPK and PI3K pathways.
Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Corrales Gutiérrez, Isabel. Hospital Virgen de Macarena; España
Fil: Sánchez Margalet, Víctor. Universidad de Sevilla; España
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
Anti-Apoptotic Effect
Leptin
Mapk And Pi3k Signal Transduction Pathways
Mdm-2
P53
Placenta
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:11336/49656
Acceder
id CONICETDig_9ea770b99f0dc54d016263493533a4e9
oai_identifier_str oai:ri.conicet.gov.ar:11336/49656
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanisms involved in p53 downregulation by leptin in trophoblastic cellsToro, Ayelen RayenPérez Pérez, AntonioCorrales Gutiérrez, IsabelSánchez Margalet, VíctorVarone, Cecilia LauraAnti-Apoptotic EffectLeptinMapk And Pi3k Signal Transduction PathwaysMdm-2P53Placentahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Leptin, a 16-kDa polypeptide hormone, is produced by the adipocyte and can also be synthesized by placenta. We previously demonstrated that leptin promotes proliferation and survival in placenta, in part mediated by the p53 pathway. In this work, we investigated the mechanisms involved in leptin down-regulation of p53 level. The human first trimester cytotrophoblastic Swan-71 cell line and human placental explants at term were used. In order to study the late phase of apoptosis, triggered by serum deprivation, experiments of DNA fragmentation were carried out. Exogenous leptin added to human placental explants, showed a decrease on DNA ladder formation and MAPK pathway is involved in this leptin effect. We also found that under serum deprivation condition, leptin decreases p53 levels and the inhibitory leptin effect is lost when cells were pretreated with 50 μM PD98059 or 10 μM LY29004; or were transfected with dominant negative mutants of intermediates of these pathways, suggesting that MAPK and PI3K signaling pathways are necessaries for leptin action. Additionally, leptin diminished Ser-46 p53 phosphorylation and this effect in placental explants was mediated by the activation of MAPK and PI3K pathways. Finally, in order to assess leptin effect on p53 half-life experiments with cycloheximide were performed and MDM-2 expression was analyzed. Leptin diminished p53 half-life and up-regulated MDM-2 expression. In summary, we provided evidence suggesting that leptin anti-apoptotic effect is mediated by MAPK and PI3K pathways.Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pérez Pérez, Antonio. Universidad de Sevilla; EspañaFil: Corrales Gutiérrez, Isabel. Hospital Virgen de Macarena; EspañaFil: Sánchez Margalet, Víctor. Universidad de Sevilla; EspañaFil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaW B Saunders Co Ltd2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49656Toro, Ayelen Rayen; Pérez Pérez, Antonio; Corrales Gutiérrez, Isabel; Sánchez Margalet, Víctor; Varone, Cecilia Laura; Mechanisms involved in p53 downregulation by leptin in trophoblastic cells; W B Saunders Co Ltd; Placenta; 36; 11; 11-2015; 1266-12750143-4004CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.placenta.2015.08.017info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0143400415300448info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:31:12Zoai:ri.conicet.gov.ar:11336/49656instacron: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 15:31:12.268CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
title Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
spellingShingle Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
Toro, Ayelen Rayen
Anti-Apoptotic Effect
Leptin
Mapk And Pi3k Signal Transduction Pathways
Mdm-2
P53
Placenta
title_short Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
title_full Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
title_fullStr Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
title_full_unstemmed Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
title_sort Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
dc.creator.none.fl_str_mv Toro, Ayelen Rayen
Pérez Pérez, Antonio
Corrales Gutiérrez, Isabel
Sánchez Margalet, Víctor
Varone, Cecilia Laura
author Toro, Ayelen Rayen
author_facet Toro, Ayelen Rayen
Pérez Pérez, Antonio
Corrales Gutiérrez, Isabel
Sánchez Margalet, Víctor
Varone, Cecilia Laura
author_role author
author2 Pérez Pérez, Antonio
Corrales Gutiérrez, Isabel
Sánchez Margalet, Víctor
Varone, Cecilia Laura
author2_role author
author
author
author
dc.subject.none.fl_str_mv Anti-Apoptotic Effect
Leptin
Mapk And Pi3k Signal Transduction Pathways
Mdm-2
P53
Placenta
topic Anti-Apoptotic Effect
Leptin
Mapk And Pi3k Signal Transduction Pathways
Mdm-2
P53
Placenta
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Leptin, a 16-kDa polypeptide hormone, is produced by the adipocyte and can also be synthesized by placenta. We previously demonstrated that leptin promotes proliferation and survival in placenta, in part mediated by the p53 pathway. In this work, we investigated the mechanisms involved in leptin down-regulation of p53 level. The human first trimester cytotrophoblastic Swan-71 cell line and human placental explants at term were used. In order to study the late phase of apoptosis, triggered by serum deprivation, experiments of DNA fragmentation were carried out. Exogenous leptin added to human placental explants, showed a decrease on DNA ladder formation and MAPK pathway is involved in this leptin effect. We also found that under serum deprivation condition, leptin decreases p53 levels and the inhibitory leptin effect is lost when cells were pretreated with 50 μM PD98059 or 10 μM LY29004; or were transfected with dominant negative mutants of intermediates of these pathways, suggesting that MAPK and PI3K signaling pathways are necessaries for leptin action. Additionally, leptin diminished Ser-46 p53 phosphorylation and this effect in placental explants was mediated by the activation of MAPK and PI3K pathways. Finally, in order to assess leptin effect on p53 half-life experiments with cycloheximide were performed and MDM-2 expression was analyzed. Leptin diminished p53 half-life and up-regulated MDM-2 expression. In summary, we provided evidence suggesting that leptin anti-apoptotic effect is mediated by MAPK and PI3K pathways.
Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Corrales Gutiérrez, Isabel. Hospital Virgen de Macarena; España
Fil: Sánchez Margalet, Víctor. Universidad de Sevilla; España
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Leptin, a 16-kDa polypeptide hormone, is produced by the adipocyte and can also be synthesized by placenta. We previously demonstrated that leptin promotes proliferation and survival in placenta, in part mediated by the p53 pathway. In this work, we investigated the mechanisms involved in leptin down-regulation of p53 level. The human first trimester cytotrophoblastic Swan-71 cell line and human placental explants at term were used. In order to study the late phase of apoptosis, triggered by serum deprivation, experiments of DNA fragmentation were carried out. Exogenous leptin added to human placental explants, showed a decrease on DNA ladder formation and MAPK pathway is involved in this leptin effect. We also found that under serum deprivation condition, leptin decreases p53 levels and the inhibitory leptin effect is lost when cells were pretreated with 50 μM PD98059 or 10 μM LY29004; or were transfected with dominant negative mutants of intermediates of these pathways, suggesting that MAPK and PI3K signaling pathways are necessaries for leptin action. Additionally, leptin diminished Ser-46 p53 phosphorylation and this effect in placental explants was mediated by the activation of MAPK and PI3K pathways. Finally, in order to assess leptin effect on p53 half-life experiments with cycloheximide were performed and MDM-2 expression was analyzed. Leptin diminished p53 half-life and up-regulated MDM-2 expression. In summary, we provided evidence suggesting that leptin anti-apoptotic effect is mediated by MAPK and PI3K pathways.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
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/11336/49656
Toro, Ayelen Rayen; Pérez Pérez, Antonio; Corrales Gutiérrez, Isabel; Sánchez Margalet, Víctor; Varone, Cecilia Laura; Mechanisms involved in p53 downregulation by leptin in trophoblastic cells; W B Saunders Co Ltd; Placenta; 36; 11; 11-2015; 1266-1275
0143-4004
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49656
identifier_str_mv Toro, Ayelen Rayen; Pérez Pérez, Antonio; Corrales Gutiérrez, Isabel; Sánchez Margalet, Víctor; Varone, Cecilia Laura; Mechanisms involved in p53 downregulation by leptin in trophoblastic cells; W B Saunders Co Ltd; Placenta; 36; 11; 11-2015; 1266-1275
0143-4004
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.placenta.2015.08.017
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0143400415300448
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
dc.publisher.none.fl_str_mv W B Saunders Co Ltd
publisher.none.fl_str_mv W B Saunders Co Ltd
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
_version_ 1846083448216748032
score 13.22299

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