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dc.contributor.author Toro, Ayelen Rayen
dc.contributor.author Maymo, Julieta Lorena
dc.contributor.author Ibarbalz, Federico Matias
dc.contributor.author Pérez Pérez, Antonio
dc.contributor.author Maskin, Bernardo
dc.contributor.author Faletti, Alicia Graciela
dc.contributor.author Sánchez Margalet, Víctor
dc.contributor.author Varone, Cecilia Laura
dc.date.available 2017-03-07T18:51:53Z
dc.date.issued 2014-06
dc.identifier.citation Toro, Ayelen Rayen; Maymo, Julieta Lorena; Ibarbalz, Federico Matias; Pérez Pérez, Antonio; Maskin, Bernardo; et al.; Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation; Public Library of Science; Plos One; 9; 6; 6-2014; e99187
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/11336/13595
dc.description.abstract Leptin, a peripheral signal synthetized by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work, we aimed to study the molecular mechanisms that mediate the survival effect of leptin in placenta. We used the human placenta choriocarcinoma BeWo and first trimester Swan-71 cell lines, as well as human placental explants. We tested the late phase of apoptosis, triggered by serum deprivation, by studying the activation of Caspase-3 and DNA fragmentation. Recombinant human leptin added to BeWo cell line and human placental explants, showed a decrease on Caspase-3 activation. These effects were dose dependent. Maximal effect was achieved at 250 ng leptin/ml. Moreover, inhibition of endogenous leptin expression with 2 µM of an antisense oligonucleotide, reversed Caspase-3 diminution. We also found that the cleavage of Poly [ADP-ribose] polymerase-1 (PARP-1) was diminished in the presence of leptin. We analyzed the presence of low DNA fragments, products from apoptotic DNA cleavage. Placental explants cultivated in the absence of serum in the culture media increased the apoptotic cleavage of DNA and this effect was prevented by the addition of 100 ng leptin/ml. Taken together these results reinforce the survival effect exerted by leptin on placental cells. To improve the understanding of leptin mechanism in regulating the process of apoptosis we determined the expression of different intermediaries in the apoptosis cascade. We found that under serum deprivation conditions, leptin increased the anti-apoptotic BCL-2 protein expression, while downregulated the pro-apoptotic BAX and BID proteins expression in Swan-71 cells and placental explants. In both models leptin augmented BCL-2/BAX ratio. Moreover we have demonstrated that p53, one of the key cell cycle-signaling proteins, is downregulated in the presence of leptin under serum deprivation. On the other hand, we determined that leptin reduced the phosphorylation of Ser-46 p53 that plays a pivotal role for apoptotic signaling by p53. Our data suggest that the observed anti-apoptotic effect of leptin in placenta is in part mediated by the p53 pathway. In conclusion, we provide evidence that demonstrates that leptin is a trophic factor for trophoblastic cells.
dc.format application/pdf
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject leptina
dc.subject placenta
dc.subject apoptosis
dc.subject p53
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-03-06T17:06:58Z
dc.journal.volume 9
dc.journal.number 6
dc.journal.pagination e99187
dc.journal.pais Estados Unidos
dc.journal.ciudad San Francisco
dc.description.fil 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; Argentina
dc.description.fil Fil: Maymo, Julieta Lorena. 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; Argentina
dc.description.fil Fil: Ibarbalz, Federico Matias. 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; Argentina
dc.description.fil Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
dc.description.fil Fil: Maskin, Bernardo. Hospital Nacional Profesor Alejandro Posadas; Argentina
dc.description.fil Fil: Faletti, Alicia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires; Argentina
dc.description.fil Fil: Sánchez Margalet, Víctor. Universidad de Sevilla; España
dc.description.fil 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; Argentina
dc.journal.title Plos One
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099187
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0099187


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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)