Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway

Autores
Pérez Pérez, Antonio; Maymo, Julieta Lorena; Dueñas, José L.; Goberna, Raimundo; Calvo. Juan Carlos; Varone, Cecilia Laura; Sánchez Margalet, Victor
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leptin (Ob), the peripheral signal produced by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the signal transduction pathways that mediate the trophic effect of leptin in placenta, by using the human placenta choriocarcinoma JEG-3 cell line, as well as trophoblastic cells from human placenta. We have assayed the early phase of apoptosis, triggered by serum deprivation, by using Annexin V-propidium iodide (PI) labeling and flow cytometric analysis, as well as the late phase of apoptosis by studying the activation of caspase-3. We have studied the major signalling pathways known to be triggered by the leptin receptor, and we have investigated the relative importance of these pathways in the effect of leptin by using pharmacological inhibitors. We have found that leptin stimulates Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway by promoting JAK-2 and STAT-3 tyrosine phosphorylation. We have also demonstrated the activation of mitogen-activated protein kinase (MAPK) pathway by studying phosphorylation of extracellular-signal regulated kinase (Erk) kinase (MEK) and Erk1/2. PI3K pathway is also triggered by leptin stimulation as assessed by the study of protein kinase B (PKB) phosphorylation. These signaling pathways were confirmed in trophoblastic cells obtained from placenta of healthy donors. The effect of leptin on JEG-3 survival was completely reversed by blocking Erk1/2 activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using wortmannin. These data suggest that the leptin antiapoptotic effect in placenta is mediated by the MAPK pathway.
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Maymo, Julieta Lorena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dueñas, José L.. Universidad de Sevilla; España
Fil: Goberna, Raimundo. Universidad de Sevilla; España
Fil: Calvo. Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Varone, Cecilia Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez Margalet, Victor. Universidad de Sevilla; España
Materia
Leptin
Leptin Receptor
Apoptosis
Placenta
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:11336/25531
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25531
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathwayPérez Pérez, AntonioMaymo, Julieta LorenaDueñas, José L.Goberna, RaimundoCalvo. Juan CarlosVarone, Cecilia LauraSánchez Margalet, VictorLeptinLeptin ReceptorApoptosisPlacentahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Leptin (Ob), the peripheral signal produced by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the signal transduction pathways that mediate the trophic effect of leptin in placenta, by using the human placenta choriocarcinoma JEG-3 cell line, as well as trophoblastic cells from human placenta. We have assayed the early phase of apoptosis, triggered by serum deprivation, by using Annexin V-propidium iodide (PI) labeling and flow cytometric analysis, as well as the late phase of apoptosis by studying the activation of caspase-3. We have studied the major signalling pathways known to be triggered by the leptin receptor, and we have investigated the relative importance of these pathways in the effect of leptin by using pharmacological inhibitors. We have found that leptin stimulates Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway by promoting JAK-2 and STAT-3 tyrosine phosphorylation. We have also demonstrated the activation of mitogen-activated protein kinase (MAPK) pathway by studying phosphorylation of extracellular-signal regulated kinase (Erk) kinase (MEK) and Erk1/2. PI3K pathway is also triggered by leptin stimulation as assessed by the study of protein kinase B (PKB) phosphorylation. These signaling pathways were confirmed in trophoblastic cells obtained from placenta of healthy donors. The effect of leptin on JEG-3 survival was completely reversed by blocking Erk1/2 activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using wortmannin. These data suggest that the leptin antiapoptotic effect in placenta is mediated by the MAPK pathway.Fil: Pérez Pérez, Antonio. Universidad de Sevilla; EspañaFil: Maymo, Julieta Lorena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dueñas, José L.. Universidad de Sevilla; EspañaFil: Goberna, Raimundo. Universidad de Sevilla; EspañaFil: Calvo. Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Varone, Cecilia Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez Margalet, Victor. Universidad de Sevilla; EspañaElsevier2008-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25531Pérez Pérez, Antonio; Maymo, Julieta Lorena; Dueñas, José L.; Goberna, Raimundo; Calvo. Juan Carlos; et al.; Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway; Elsevier; Archives of Biochemistry and Biophysics; 477; 2; 9-2008; 390-3950003-98611096-0384CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S000398610800310Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2008.06.015info:eu-repo/semantics/altIdentifier/pmid/18619412info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:08Zoai:ri.conicet.gov.ar:11336/25531instacron: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:34982025-09-03 10:03:08.846CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
title Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
spellingShingle Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
Pérez Pérez, Antonio
Leptin
Leptin Receptor
Apoptosis
Placenta
title_short Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
title_full Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
title_fullStr Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
title_full_unstemmed Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
title_sort Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway
dc.creator.none.fl_str_mv Pérez Pérez, Antonio
Maymo, Julieta Lorena
Dueñas, José L.
Goberna, Raimundo
Calvo. Juan Carlos
Varone, Cecilia Laura
Sánchez Margalet, Victor
author Pérez Pérez, Antonio
author_facet Pérez Pérez, Antonio
Maymo, Julieta Lorena
Dueñas, José L.
Goberna, Raimundo
Calvo. Juan Carlos
Varone, Cecilia Laura
Sánchez Margalet, Victor
author_role author
author2 Maymo, Julieta Lorena
Dueñas, José L.
Goberna, Raimundo
Calvo. Juan Carlos
Varone, Cecilia Laura
Sánchez Margalet, Victor
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Leptin
Leptin Receptor
Apoptosis
Placenta
topic Leptin
Leptin Receptor
Apoptosis
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 (Ob), the peripheral signal produced by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the signal transduction pathways that mediate the trophic effect of leptin in placenta, by using the human placenta choriocarcinoma JEG-3 cell line, as well as trophoblastic cells from human placenta. We have assayed the early phase of apoptosis, triggered by serum deprivation, by using Annexin V-propidium iodide (PI) labeling and flow cytometric analysis, as well as the late phase of apoptosis by studying the activation of caspase-3. We have studied the major signalling pathways known to be triggered by the leptin receptor, and we have investigated the relative importance of these pathways in the effect of leptin by using pharmacological inhibitors. We have found that leptin stimulates Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway by promoting JAK-2 and STAT-3 tyrosine phosphorylation. We have also demonstrated the activation of mitogen-activated protein kinase (MAPK) pathway by studying phosphorylation of extracellular-signal regulated kinase (Erk) kinase (MEK) and Erk1/2. PI3K pathway is also triggered by leptin stimulation as assessed by the study of protein kinase B (PKB) phosphorylation. These signaling pathways were confirmed in trophoblastic cells obtained from placenta of healthy donors. The effect of leptin on JEG-3 survival was completely reversed by blocking Erk1/2 activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using wortmannin. These data suggest that the leptin antiapoptotic effect in placenta is mediated by the MAPK pathway.
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Maymo, Julieta Lorena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dueñas, José L.. Universidad de Sevilla; España
Fil: Goberna, Raimundo. Universidad de Sevilla; España
Fil: Calvo. Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Varone, Cecilia Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez Margalet, Victor. Universidad de Sevilla; España
description Leptin (Ob), the peripheral signal produced by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the signal transduction pathways that mediate the trophic effect of leptin in placenta, by using the human placenta choriocarcinoma JEG-3 cell line, as well as trophoblastic cells from human placenta. We have assayed the early phase of apoptosis, triggered by serum deprivation, by using Annexin V-propidium iodide (PI) labeling and flow cytometric analysis, as well as the late phase of apoptosis by studying the activation of caspase-3. We have studied the major signalling pathways known to be triggered by the leptin receptor, and we have investigated the relative importance of these pathways in the effect of leptin by using pharmacological inhibitors. We have found that leptin stimulates Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway by promoting JAK-2 and STAT-3 tyrosine phosphorylation. We have also demonstrated the activation of mitogen-activated protein kinase (MAPK) pathway by studying phosphorylation of extracellular-signal regulated kinase (Erk) kinase (MEK) and Erk1/2. PI3K pathway is also triggered by leptin stimulation as assessed by the study of protein kinase B (PKB) phosphorylation. These signaling pathways were confirmed in trophoblastic cells obtained from placenta of healthy donors. The effect of leptin on JEG-3 survival was completely reversed by blocking Erk1/2 activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using wortmannin. These data suggest that the leptin antiapoptotic effect in placenta is mediated by the MAPK pathway.
publishDate 2008
dc.date.none.fl_str_mv 2008-09
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/11336/25531
Pérez Pérez, Antonio; Maymo, Julieta Lorena; Dueñas, José L.; Goberna, Raimundo; Calvo. Juan Carlos; et al.; Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway; Elsevier; Archives of Biochemistry and Biophysics; 477; 2; 9-2008; 390-395
0003-9861
1096-0384
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25531
identifier_str_mv Pérez Pérez, Antonio; Maymo, Julieta Lorena; Dueñas, José L.; Goberna, Raimundo; Calvo. Juan Carlos; et al.; Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway; Elsevier; Archives of Biochemistry and Biophysics; 477; 2; 9-2008; 390-395
0003-9861
1096-0384
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S000398610800310X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2008.06.015
info:eu-repo/semantics/altIdentifier/pmid/18619412
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.13397

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