Artículo

Toro, A.R.; Pérez-Pérez, A.; Corrales Gutiérrez, I.; Sánchez-Margalet, V.; Varone, C.L. "Mechanisms involved in p53 downregulation by leptin in trophoblastic cells" (2015) Placenta. 36(11):1266-1275
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Abstract:

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.

Registro:

Documento: Artículo
Título:Mechanisms involved in p53 downregulation by leptin in trophoblastic cells
Autor:Toro, A.R.; Pérez-Pérez, A.; Corrales Gutiérrez, I.; Sánchez-Margalet, V.; Varone, C.L.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain
Palabras clave: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
Año:2015
Volumen:36
Número:11
Página de inicio:1266
Página de fin:1275
DOI: http://dx.doi.org/10.1016/j.placenta.2015.08.017
Título revista:Placenta
Título revista abreviado:Placenta
ISSN:01434004
CODEN:PLACD
CAS: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
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n11_p1266_Toro

Referencias:

  • Maymo, J.L., Perez, A.P., Gambino, Y., Calvo, J.C., Sanchez-Margalet, V., Varone, C.L., Review: Leptin gene expression in the placenta-regulation of a key hormone in trophoblast proliferation and survival (2011) Placenta, 32, pp. S146-S153
  • Levy, R., Nelson, D.M., To be, or not to be, that is the question. Apoptosis in human trophoblast (2000) Placenta, 21, pp. 1-13
  • Heazell, A.E., Crocker, I.P., Live and let die - Regulation of villous trophoblast apoptosis in normal and abnormal pregnancies (2008) Placenta, 29, pp. 772-783
  • Prives, C., Hall, P.A., The p53 pathway (1999) J. Pathol., 187, pp. 112-126
  • Meek, D.W., Anderson, C.W., Posttranslational modification of p53: Cooperative integrators of function (2009) Cold Spring Harb. Perspect. Biol., 1, p. a000950
  • Hock, A.K., Vousden, K.H., The role of ubiquitin modification in the regulation of p53 (2014) Biochim. Biophys. Acta, 1843, pp. 137-149
  • Wade, M., Li, Y.C., Wahl, G.M., MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) Nat. Rev. Cancer, 13, pp. 83-96
  • Pant, V., Lozano, G., Limiting the power of p53 through the ubiquitin proteasome pathway (2015) Genes Dev., 28, pp. 1739-1751
  • Prives, C., Signaling to p53: Breaking the MDM2-p53 circuit (1998) Cell, 95, pp. 5-8
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J.M., Positional cloning of the mouse obese gene and its human homologue (1994) Nature, 372, pp. 425-432
  • Flier, J.S., The adipocyte: Storage depot or node on the energy information superhighway? (1995) Cell, 80, pp. 15-18
  • Sagawa, N., Yura, S., Itoh, H., Mise, H., Kakui, K., Korita, D., Takemura, M., Fujii, S., Role of leptin in pregnancy-a review (2002) Placenta, 23, pp. S80-S86
  • Cervero, A., Horcajadas, J.A., Dominguez, F., Pellicer, A., Simon, C., Leptin system in embryo development and implantation: A protein in search of a function (2005) Reprod. Biomed. Online, 10, pp. 217-223
  • Henson, M.C., Castracane, V.D., Leptin in pregnancy: An update (2006) Biol. Reprod., 74, pp. 218-229
  • Madej, T., Boguski, M.S., Bryant, S.H., Threading analysis suggests that the obese gene product may be a helical cytokine (1995) FEBS Lett., 373, pp. 13-18
  • Tartaglia, L.A., The leptin receptor (1997) J. Biol. Chem., 272, pp. 6093-6096
  • Tessier, D.R., Ferraro, Z.M., Gruslin, A., Role of leptin in pregnancy: Consequences of maternal obesity (2013) Placenta, 34, pp. 205-211
  • Bjorbak, C., Lavery, H.J., Bates, S.H., Olson, R.K., Davis, S.M., Flier, J.S., Myers, M.G., Jr., SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985 (2000) J. Biol. Chem., 275, pp. 40649-40657
  • Challier, J., Galtier, M., Bintein, T., Cortez, A., Lepercq, J., Hauguel-De Mouzon, S., Placental leptin receptor isoforms in normal and pathological pregnancies (2003) Placenta, 24, pp. 92-99
  • Perez-Perez, A., Maymo, J., Duenas, J.L., Goberna, R., Calvo, J.C., Varone, C., Sanchez-Margalet, V., Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway (2008) Arch. Biochem. Biophys., 477, pp. 390-395
  • Henson, M.C., Swan, K.F., O'Neil, J.S., Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term (1998) Obstet. Gynecol., 92, pp. 1020-1028
  • Gambino, Y.P., Maymo, J.L., Perez-Perez, A., Dueñas, J.L., Sánchez-Margalet, V., Calvo, J.C., Varone, C.L., 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions (2010) Biol. Reprod., 83, pp. 42-51
  • Gambino, Y.P., Maymo, J.L., Perez Perez, A., Calvo, J.L., Sánchez-Margalet, V., Varone, C.L., Elsevier trophoblast research award lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells - Focus on leptin expression (2012) Placenta, 33, pp. S63-S70
  • Perez-Perez, A., Maymo, J., Gambino, Y., Guadix, P., Duenas, J.L., Varone, C., Sanchez-Margalet, V., Insulin enhances leptin expression in human trophoblastic cells (2013) Biol. Reprod., 89, p. 20
  • Maymo, J.L., Perez Perez, A., Sanchez-Margalet, V., Duenas, J.L., Calvo, J.C., Varone, C.L., Up-regulation of placental leptin by human chorionic gonadotropin (2009) Endocrinology, 150, pp. 304-313
  • Maymo, J.L., Perez Perez, A., Duenas, J.L., Calvo, J.C., Sanchez-Margalet, V., Varone, C.L., Regulation of placental leptin expression by cyclic adenosine 5'-monophosphate involves cross talk between protein kinase A and mitogen-activated protein kinase signaling pathways (2010) Endocrinology, 151, pp. 3738-3751
  • Grosfeld, A., Turban, S., Andre, J., Cauzac, M., Challier, J.C., Hauguel-De Mouzon, S., Guerre-Millo, M., Transcriptional effect of hypoxia on placental leptin (2001) FEBS Lett., 502, pp. 122-126
  • Bajoria, R., Sooranna, S.R., Ward, B.S., Chatterjee, R., Prospective function of placental leptin at maternal-fetal interface (2002) Placenta, 23, pp. 103-115
  • Laivuori, H., Gallaher, M.J., Collura, L., Crombleholme, W.R., Markovic, N., Rajakumar, A., Hubel, C.A., Powers, R.W., Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia (2006) Mol. Hum. Reprod., 12, pp. 551-556
  • Magarinos, M.P., Sanchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L., Leptin promotes cell proliferation and survival of trophoblastic cells (2007) Biol. Reprod., 76, pp. 203-210
  • Perez-Perez, A., Maymo, J., Gambino, Y., Duenas, J.L., Goberna, R., Varone, C., Sanchez-Margalet, V., Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells (2009) Biol. Reprod., 81, pp. 826-832
  • Perez-Perez, A., Gambino, Y., Maymo, J., Goberna, R., Fabiani, F., Varone, C., Sanchez-Margalet, V., MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells (2010) Biochem. Biophys. Res. Commun., 396, pp. 956-960
  • Toro, A.R., Maymo, J.L., Ibarbalz, F.M., Perez Perez, A., Maskin, B., Faletti, A.G., Sanchez Margalet, V., Varone, C.L., Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation (2014) PLoS One, 9, p. e99187
  • Shawn, L., Straszewski-Chavez, S.L., Abrahams, V.M., Alvero, A.B., Aldo, P.B., Ma, Y., Guller, S., Mor, G., The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71 (2009) Placenta, 30, pp. 939-948
  • Ramhorst, R., Fraccaroli, L., Aldo, P., Alvero, A.B., Cardenas, I., Leiros, C.P., Mor, G., Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells (2012) Am. J. Reprod. Immunol., 67, pp. 17-27
  • Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal. Biochem., 72, pp. 248-254
  • Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method (2001) Methods, 25, pp. 402-408
  • Masuzaki, H., Ogawa, Y., Isse, N., Satoh, N., Okazaki, T., Shigemoto, M., Mori, K., Yoshimasa, Y., Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue (1995) Diabetes, 44, pp. 855-858
  • Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., Burn, P., Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks (1995) Science (New York N. Y.), 269, pp. 546-549
  • Barrientos, G., Toro, A., Moschansky, P., Cohen, M., Garcia, M.G., Rose, M., Maskin, B., Varone, C.L., Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways (2015) Placenta, 36, pp. 419-426
  • Ashworth, C.J., Hoggard, N., Thomas, L., Mercer, J.G., Wallace, J.M., Lea, R.G., Placental leptin (2000) Rev. Reprod., 5, pp. 18-24
  • Nelson, S.M., Coan, P.M., Burton, G.J., Lindsay, R.S., Placental structure in type 1 diabetes: Relation to fetal insulin, leptin, and IGF-I (2009) Diabetes, 58, pp. 2634-2641
  • Iciek, R., Wender-Ozegowska, E., Zawiejska, A., Mikolajczak, P., Mrozikiewicz, P.M., Pietryga, M., Brazert, J., Placental leptin and its receptor genes expression in pregnancies complicated by type 1 diabetes (2013) J. Physiol. Pharmacol., 64, pp. 579-585
  • Poston, L., Leptin and preeclampsia (2002) Semin. Reprod. Med., 20, pp. 131-138
  • Perez-Perez, A., Sanchez-Jimenez, F., Maymo, J., Duenas, J.L., Varone, C., Sanchez-Margalet, V., Role of leptin in female reproduction (2015) Clin. Chem. Lab. Med., 53, pp. 15-28
  • Saxena, N.K., Titus, M.A., Ding, X., Floyd, J., Srinivasan, S., Sitaraman, S.V., Anania, F.A., Leptin as a novel profibrogenic cytokine in hepatic stellate cells: Mitogenesis and inhibition of apoptosis mediated by extracellular regulated kinase (Erk) and Akt phosphorylation (2004) Faseb J., 18, pp. 1612-1614
  • Bruno, A., Conus, S., Schmid, I., Simon, H.U., Apoptotic pathways are inhibited by leptin receptor activation in neutrophils (2005) J. Immunol., 174, pp. 8090-8096
  • Najib, S., Sanchez-Margalet, V., Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway (2002) Cell. Immunol., 220, pp. 143-149
  • Vogelstein, B., Lane, D., Levine, A.J., Surfing the p53 network (2000) Nature, 408, pp. 307-310
  • Sharp, A.N., Heazell, A.E., Baczyk, D., Dunk, C.E., Lacey, H.A., Jones, C.J., Perkins, J.E., Crocker, I.P., Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast (2014) PLoS One, 9, p. e87621
  • Levy, R., Smith, S.D., Yusuf, K., Huettner, P.C., Kraus, F.T., Sadovsky, Y., Nelson, D.M., Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression (2002) Am. J. Obstet.Gynecol., 186, pp. 1056-1061
  • Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Taya, Y., P53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53 (2000) Cell, 102, pp. 849-862
  • Quenby, S., Brazeau, C., Drakeley, A., Lewis-Jones, D.I., Vince, G., Oncogene and tumour suppressor gene products during trophoblast differentiation in the first trimester (1998) Mol. Hum. Reprod., 4, pp. 477-481
  • Marzusch, K., Ruck, P., Horny, H.P., Dietl, J., Kaiserling, E., Expression of the p53 tumour suppressor gene in human placenta: An immunohistochemical study (1995) Placenta, 16, pp. 101-104
  • Barak, Y., Juven, T., Haffner, R., Oren, M., Mdm2 expression is induced by wild type p53 activity (1993) EMBO J., 12, pp. 461-468
  • Saucedo, L.J., Carstens, B.P., Seavey, S.E., Albee, L.D., II, Perry, M.E., Regulation of transcriptional activation of mdm2 gene by p53 in response to UV radiation (1998) Cell Growth Differ., 9, pp. 119-130
  • Eischen, C.M., Lozano, G., The Mdm network and its regulation of p53 activities: A rheostat of cancer risk (2014) Hum. Mutat., 35, pp. 728-737
  • Li, M., Brooks, C.L., Wu-Baer, F., Chen, D., Baer, R., Gu, W., Mono- versus polyubiquitination: Differential control of p53 fate by Mdm2 (2003) Science, 302, pp. 1972-1975

Citas:

---------- APA ----------
Toro, A.R., Pérez-Pérez, A., Corrales Gutiérrez, I., Sánchez-Margalet, V. & Varone, C.L. (2015) . Mechanisms involved in p53 downregulation by leptin in trophoblastic cells. Placenta, 36(11), 1266-1275.
http://dx.doi.org/10.1016/j.placenta.2015.08.017
---------- CHICAGO ----------
Toro, A.R., Pérez-Pérez, A., Corrales Gutiérrez, I., Sánchez-Margalet, V., Varone, C.L. "Mechanisms involved in p53 downregulation by leptin in trophoblastic cells" . Placenta 36, no. 11 (2015) : 1266-1275.
http://dx.doi.org/10.1016/j.placenta.2015.08.017
---------- MLA ----------
Toro, A.R., Pérez-Pérez, A., Corrales Gutiérrez, I., Sánchez-Margalet, V., Varone, C.L. "Mechanisms involved in p53 downregulation by leptin in trophoblastic cells" . Placenta, vol. 36, no. 11, 2015, pp. 1266-1275.
http://dx.doi.org/10.1016/j.placenta.2015.08.017
---------- VANCOUVER ----------
Toro, A.R., Pérez-Pérez, A., Corrales Gutiérrez, I., Sánchez-Margalet, V., Varone, C.L. Mechanisms involved in p53 downregulation by leptin in trophoblastic cells. Placenta. 2015;36(11):1266-1275.
http://dx.doi.org/10.1016/j.placenta.2015.08.017