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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| Otros Autores: | , , , |
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| Publicado: |
W.B. Saunders Ltd
2015
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| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
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| LEADER | 18260caa a22017537a 4500 | ||
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| 003 | AR-BaUEN | ||
| 005 | 20230518204326.0 | ||
| 008 | 190411s2015 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-84947038203 | |
| 024 | 7 | |2 cas |a 2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; Leptin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a PLACD | ||
| 100 | 1 | |a Toro, A.R. | |
| 245 | 1 | 0 | |a Mechanisms involved in p53 downregulation by leptin in trophoblastic cells |
| 260 | |b W.B. Saunders Ltd |c 2015 | ||
| 270 | 1 | 0 | |m Varone, C.L.; Química Biológica Ciudad Universitaria, Pabellón 2, piso 4, Argentina; email: cvarone@qb.fcen.uba.ar |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a 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. |l eng | |
| 536 | |a Detalles de la financiación: Fondazione ART per la Ricerca sui Trapianti, ART | ||
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires | ||
| 536 | |a Detalles de la financiación: Secretaría de Ciencia y Técnica, Universidad de Buenos Aires | ||
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PS09/00119, PICT 2012-1366 | ||
| 536 | |a Detalles de la financiación: Instituto de Salud Carlos III, CM07/00025 | ||
| 536 | |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas | ||
| 536 | |a Detalles de la financiación: ART is supported by a CONICET fellowship . APP is a research fellow supported by the Instituto de Salud Carlos III ( CM07/00025 ). This project was supported by the Universidad de Buenos Aires (UBACYT), the ANPCyT ( PICT 2012-1366 ) and the Instituto de Salud Carlos III ( PS09/00119 ), Spain. | ||
| 593 | |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina | ||
| 593 | |a Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain | ||
| 690 | 1 | 0 | |a ANTI-APOPTOTIC EFFECT |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a MAPK AND PI3K SIGNAL TRANSDUCTION PATHWAYS |
| 690 | 1 | 0 | |a MDM-2 |
| 690 | 1 | 0 | |a P53 |
| 690 | 1 | 0 | |a 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a LY 29004 |
| 690 | 1 | 0 | |a MITOGEN ACTIVATED PROTEIN KINASE |
| 690 | 1 | 0 | |a PHOSPHATIDYLINOSITOL 3 KINASE |
| 690 | 1 | 0 | |a PROTEIN INHIBITOR |
| 690 | 1 | 0 | |a PROTEIN P53 |
| 690 | 1 | 0 | |a UNCLASSIFIED DRUG |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a PHOSPHATIDYLINOSITOL 3 KINASE |
| 690 | 1 | 0 | |a PROTEIN MDM2 |
| 690 | 1 | 0 | |a PROTEIN P53 |
| 690 | 1 | 0 | |a APOPTOSIS |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a DNA FRAGMENTATION |
| 690 | 1 | 0 | |a DOWN REGULATION |
| 690 | 1 | 0 | |a ENZYME ACTIVITY |
| 690 | 1 | 0 | |a EXPLANT |
| 690 | 1 | 0 | |a FIRST TRIMESTER PREGNANCY |
| 690 | 1 | 0 | |a HALF LIFE TIME |
| 690 | 1 | 0 | |a HUMAN |
| 690 | 1 | 0 | |a HUMAN CELL |
| 690 | 1 | 0 | |a HUMAN TISSUE |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a PROTEIN PHOSPHORYLATION |
| 690 | 1 | 0 | |a REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION |
| 690 | 1 | 0 | |a SIGNAL TRANSDUCTION |
| 690 | 1 | 0 | |a TRANSIENT TRANSFECTION |
| 690 | 1 | 0 | |a TROPHOBLAST |
| 690 | 1 | 0 | |a WESTERN BLOTTING |
| 690 | 1 | 0 | |a CELL LINE |
| 690 | 1 | 0 | |a CELL PROLIFERATION |
| 690 | 1 | 0 | |a METABOLISM |
| 690 | 1 | 0 | |a TROPHOBLAST |
| 690 | 1 | 0 | |a APOPTOSIS |
| 690 | 1 | 0 | |a CELL LINE |
| 690 | 1 | 0 | |a CELL PROLIFERATION |
| 690 | 1 | 0 | |a HUMANS |
| 690 | 1 | 0 | |a LEPTIN |
| 690 | 1 | 0 | |a MAP KINASE SIGNALING SYSTEM |
| 690 | 1 | 0 | |a PHOSPHATIDYLINOSITOL 3-KINASES |
| 690 | 1 | 0 | |a PROTO-ONCOGENE PROTEINS C-MDM2 |
| 690 | 1 | 0 | |a TROPHOBLASTS |
| 690 | 1 | 0 | |a TUMOR SUPPRESSOR PROTEIN P53 |
| 650 | 1 | 7 | |2 spines |a PLACENTA |
| 653 | 0 | 0 | |a ly 29004; pd 98059 |
| 700 | 1 | |a Pérez-Pérez, A. | |
| 700 | 1 | |a Corrales Gutiérrez, I. | |
| 700 | 1 | |a Sánchez-Margalet, V. | |
| 700 | 1 | |a Varone, C.L. | |
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