Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
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 dow...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n11_p1266_Toro http://hdl.handle.net/20.500.12110/paper_01434004_v36_n11_p1266_Toro |
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paper:paper_01434004_v36_n11_p1266_Toro2023-06-08T15:11:50Z Mechanisms involved in p53 downregulation by leptin in trophoblastic cells Varone, Cecilia Laura Anti-apoptotic effect Leptin MAPK and PI3K signal transduction pathways MDM-2 p53 Placenta 2 (2 amino 3 methoxyphenyl)chromone leptin ly 29004 mitogen activated protein kinase phosphatidylinositol 3 kinase protein inhibitor protein p53 unclassified drug leptin phosphatidylinositol 3 kinase protein MDM2 protein p53 apoptosis Article DNA fragmentation down regulation enzyme activity explant first trimester pregnancy half life time human human cell human tissue priority journal protein phosphorylation reverse transcription polymerase chain reaction signal transduction transient transfection trophoblast Western blotting cell line cell proliferation metabolism trophoblast Apoptosis Cell Line Cell Proliferation Humans Leptin MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-mdm2 Trophoblasts Tumor Suppressor Protein p53 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. © 2015 Elsevier Ltd. All rights reserved. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n11_p1266_Toro http://hdl.handle.net/20.500.12110/paper_01434004_v36_n11_p1266_Toro |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Anti-apoptotic effect Leptin MAPK and PI3K signal transduction pathways MDM-2 p53 Placenta 2 (2 amino 3 methoxyphenyl)chromone leptin ly 29004 mitogen activated protein kinase phosphatidylinositol 3 kinase protein inhibitor protein p53 unclassified drug leptin phosphatidylinositol 3 kinase protein MDM2 protein p53 apoptosis Article DNA fragmentation down regulation enzyme activity explant first trimester pregnancy half life time human human cell human tissue priority journal protein phosphorylation reverse transcription polymerase chain reaction signal transduction transient transfection trophoblast Western blotting cell line cell proliferation metabolism trophoblast Apoptosis Cell Line Cell Proliferation Humans Leptin MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-mdm2 Trophoblasts Tumor Suppressor Protein p53 |
| spellingShingle |
Anti-apoptotic effect Leptin MAPK and PI3K signal transduction pathways MDM-2 p53 Placenta 2 (2 amino 3 methoxyphenyl)chromone leptin ly 29004 mitogen activated protein kinase phosphatidylinositol 3 kinase protein inhibitor protein p53 unclassified drug leptin phosphatidylinositol 3 kinase protein MDM2 protein p53 apoptosis Article DNA fragmentation down regulation enzyme activity explant first trimester pregnancy half life time human human cell human tissue priority journal protein phosphorylation reverse transcription polymerase chain reaction signal transduction transient transfection trophoblast Western blotting cell line cell proliferation metabolism trophoblast Apoptosis Cell Line Cell Proliferation Humans Leptin MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-mdm2 Trophoblasts Tumor Suppressor Protein p53 Varone, Cecilia Laura Mechanisms involved in p53 downregulation by leptin in trophoblastic cells |
| topic_facet |
Anti-apoptotic effect Leptin MAPK and PI3K signal transduction pathways MDM-2 p53 Placenta 2 (2 amino 3 methoxyphenyl)chromone leptin ly 29004 mitogen activated protein kinase phosphatidylinositol 3 kinase protein inhibitor protein p53 unclassified drug leptin phosphatidylinositol 3 kinase protein MDM2 protein p53 apoptosis Article DNA fragmentation down regulation enzyme activity explant first trimester pregnancy half life time human human cell human tissue priority journal protein phosphorylation reverse transcription polymerase chain reaction signal transduction transient transfection trophoblast Western blotting cell line cell proliferation metabolism trophoblast Apoptosis Cell Line Cell Proliferation Humans Leptin MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-mdm2 Trophoblasts Tumor Suppressor Protein p53 |
| 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. © 2015 Elsevier Ltd. All rights reserved. |
| author |
Varone, Cecilia Laura |
| author_facet |
Varone, Cecilia Laura |
| author_sort |
Varone, Cecilia Laura |
| title |
Mechanisms involved in p53 downregulation by leptin in trophoblastic cells |
| 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 |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n11_p1266_Toro http://hdl.handle.net/20.500.12110/paper_01434004_v36_n11_p1266_Toro |
| work_keys_str_mv |
AT varonececilialaura mechanismsinvolvedinp53downregulationbyleptinintrophoblasticcells |
| _version_ |
1768546202301759488 |