MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells

Leptin, the LEP gene product, is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy. Thus, we have recently described the antiapoptotic and trophic effect of leptin on choriocarcinoma cell line JEG-3, stimulating DNA and protein...

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Autor principal: Pérez-Pérez, A.
Otros Autores: Gambino, Y., Maymó, J., Goberna, R., Fabiani, F., Varone, C., Sánchez-Margalet, V.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2010
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Acceso en línea:Registro en Scopus
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100 1 |a Pérez-Pérez, A. 
245 1 0 |a MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells 
260 |c 2010 
270 1 0 |m Sánchez-Margalet, V.; Department of Clinical Biochemistry, Virgen Macarena University Hospital, University of SevilleSpain; email: margalet@us.es 
506 |2 openaire  |e Política editorial 
504 |a Archanco, M., Muruzabal, F.J., Llopiz, D., Garayoa, M., Gomez-Ambrosi, J., Fruhbeck, G., Burrell, M.A., Leptin expression in the rat ovary depends on estrous cycle (2003) J. Histochem. Cytochem., 51, pp. 1269-1277 
504 |a Karlsson, C., Lindell, K., Svensson, E., Bergh, C., Lind, P., Billig, H., Carlsson, L.M., Carlsson, B., Expression of functional leptin receptors in the human ovary (1997) J. Clin. Endocrinol. Metab., 82, pp. 4144-4148 
504 |a Loffler, S., Aust, G., Kohler, U., Spanel-Borowski, K., Evidence of leptin expression in normal and polycystic human ovaries (2001) Mol. Hum. Reprod., 7, pp. 1143-1149 
504 |a Ryan, N.K., Van der Hoek, K.H., Robertson, S.A., Norman, R.J., Leptin and leptin receptor expression in the rat ovary (2003) Endocrinology, 144, pp. 5006-5013 
504 |a Spicer, L.J., Francisco, C.C., Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis (1998) Biol. Reprod., 58, pp. 207-212 
504 |a Caprio, M., Fabbrini, E., Ricci, G., Basciani, S., Gnessi, L., Arizzi, M., Carta, A.R., Fabbri, A., Ontogenesis of leptin receptor in rat Leydig cells (2003) Biol. Reprod., 68, pp. 1199-1207 
504 |a Hoggard, N., Hunter, L., Duncan, J.S., Williams, L.M., Trayhurn, P., Mercer, J.G., Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta (1997) Proc. Natl. Acad. Sci. USA, 94, pp. 11073-11078 
504 |a Tena-Sempere, M., Barreiro, M.L., Leptin in male reproduction: the testis paradigm (2002) Mol. Cell Endocrinol., 188, pp. 9-13 
504 |a Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Nakao, K., Nonadipose tissue production of leptin:leptin as a novel placenta-derived hormone in humans (1997) Nat. Med., 3, pp. 1029-1033 
504 |a 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 (SUPPL. A), pp. S80-S86 
504 |a Bowen, J.M., Chamley, L., Keelan, J.A., Mitchell, M.D., Cytokines of the placenta and extra-placental membranes: roles and regulation during human pregnancy and parturition (2002) Placenta, 23, pp. 257-273 
504 |a Bowen, J.M., Chamley, L., Mitchell, M.D., Keelan, J.A., Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion and roles in establishment of pregnancy in women (2002) Placenta, 23, pp. 239-256 
504 |a Cervero, A., Horcajadas, J.A., MartIn, J., Pellicer, A., Simon, C., The leptin system during human endometrial receptivity and preimplantation development (2004) J. Clin. Endocrinol. Metab., 89, pp. 2442-2451 
504 |a Henson, M.C., Castracane, V.D., Leptin in pregnancy: an update (2006) Biol. Reprod., 74, pp. 218-229 
504 |a Reitman, M.L., Bi, S., Marcus-Samuels, B., Gavrilova, O., Leptin and its role in pregnancy and fetal development - an overview (2001) Biochem. Soc. Trans., 29, pp. 68-72 
504 |a Kauma, S.W., Cytokines in implantation (2000) J. Reprod. Fertil. Suppl., 55, pp. 31-42 
504 |a Castellucci, M., De, M.R., Meisser, A., Cancello, R., Monsurro, V., Islami, D., Sarzani, R., Bischof, P., Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion (2000) Mol. Hum. Reprod., 6, pp. 951-958 
504 |a 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 
504 |a Fitzgerald, J.S., Busch, S., Wengenmayer, T., Foerster, K., de la, M.T., Poehlmann, T.G., Markert, U.R., Signal transduction in trophoblast invasion (2005) Chem. Immunol. Allergy, 88, pp. 181-199 
504 |a Maymo, J.L., Perez, P.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 
504 |a Dajani, O.F., Sandnes, D., Melien, O., Rezvani, F., Nilssen, L.S., Thoresen, G.H., Christoffersen, T., Role of diacylglycerol (DAG) in hormonal induction of S phase in hepatocytes: the DAG-dependent protein kinase C pathway is not activated by epidermal growth factor (EGF), but is involved in mediating the enhancement of responsiveness to EGF by vasopressin, angiotensin II, and norepinephrine (1999) J. Cell Physiol., 180, pp. 203-214 
504 |a Kaneko, A., Hayashi, N., Tsubouchi, H., Tanaka, Y., Ito, T., Sasaki, Y., Fusamoto, H., Kamada, T., Intracellular calcium as a second messenger for human hepatocyte growth factor in hepatocytes (1992) Hepatology, 15, pp. 1173-1178 
504 |a Morrell, N.W., Upton, P.D., Kotecha, S., Huntley, A., Yacoub, M.H., Polak, J.M., Wharton, J., Angiotensin II activates MAPK and stimulates growth of human pulmonary artery smooth muscle via AT1 receptors (1999) Am. J. Physiol., 277, pp. L440-L448 
504 |a Burnett, P.E., Barrow, R.K., Cohen, N.A., Snyder, S.H., Sabatini, D.M., RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 (1998) Proc. Natl. Acad. Sci. USA, 95, pp. 1432-1437 
504 |a 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 
504 |a Proud, C.G., Denton, R.M., Molecular mechanisms for the control of translation by insulin (1997) Biochem. J., 328, pp. 329-341 
504 |a Lin, T.A., Kong, X., Haystead, T.A., Pause, A., Belsham, G., Sonenberg, N., Lawrence Jr., J.C., PHAS-I as a link between mitogen-activated protein kinase and translation initiation (1994) Science, 266, pp. 653-656 
504 |a Kleijn, M., Scheper, G.C., Voorma, H.O., Thomas, A.A., Regulation of translation initiation factors by signal transduction (1998) Eur. J. Biochem., 253, pp. 531-544 
504 |a Minich, W.B., Balasta, M.L., Goss, D.J., Rhoads, R.E., Chromatographic resolution of in vivo phosphorylated and nonphosphorylated eukaryotic translation initiation factor eIF-4E: increased cap affinity of the phosphorylated form (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 7668-7672 
504 |a Gonzalez-Yanes, C., Sanchez-Margalet, V., Pancreastatin, a chromogranin A-derived peptide, activates protein synthesis signaling cascade in rat adipocytes (2002) Biochem. Biophys. Res. Commun., 299, pp. 525-531 
504 |a Sanchez-Margalet, V., Gonzalez-Yanes, C., Najib, S., Pancreastatin, a chromogranin A-derived peptide, inhibits DNA and protein synthesis by producing nitric oxide in HTC rat hepatoma cells (2001) J. Hepatol., 35, pp. 80-85 
504 |a Jansson, N., Greenwood, S.L., Johansson, B.R., Powell, T.L., Jansson, T., Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments (2003) J. Clin. Endocrinol. Metab., 88, pp. 1205-1211 
504 |a von Versen-Hoynck, F., Rajakumar, A., Parrott, M.S., Powers, R.W., Leptin affects system A amino acid transport activity in the human placenta: evidence for STAT3 dependent mechanisms (2009) Placenta, 30, pp. 361-367 
504 |a Bajoria, R., Sooranna, S.R., Ward, B.S., Chatterjee, R., (2002) Prospective function of placental leptin at maternal-fetal interface, , in, Anonymous pp. 103-115 
504 |a Hauguel-De, M.S., Lepercq, J., Placental leptin and pregnancy pathologies (2001) Gynecol. Obstet. Fertil., 29, pp. 534-537 
504 |a Sooranna, S.R., Ward, S., Bajoria, R., Fetal leptin influences birth weight in twins with discordant growth (2001) Pediatr. Res., 49, pp. 667-672 
504 |a Coso, O.A., Chiariello, M., Yu, J.C., Teramoto, H., Crespo, P., Xu, N., Miki, T., Gutkind, J.S., The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway (1995) Cell, 81, pp. 1137-1146 
504 |a Monjo, M., Pujol, E., Roca, P., Alpha2- to beta3-Adrenoceptor switch in 3T3-L1 preadipocytes and adipocytes: modulation by testosterone, 17beta-estradiol, and progesterone (2005) Am. J. Physiol Endocrinol. Metab., 289, pp. E145-E150 
504 |a Popovic, V., Casanueva, F.F., Leptin, nutrition and reproduction: new insights (2002) Hormones (Athens.), 1, pp. 204-217 
504 |a Martin-Romero, C., Sanchez-Margalet, V., Human leptin activates PI3K and MAPK pathways in human peripheral blood mononuclear cells: possible role of Sam68 (2001) Cell Immunol., 212, pp. 83-91 
504 |a Bjorbaek, C., Uotani, S., da, S.B., Flier, J.S., Divergent signaling capacities of the long and short isoforms of the leptin receptor (1997) J. Biol. Chem., 272, pp. 32686-32695 
504 |a Tanabe, K., Okuya, S., Tanizawa, Y., Matsutani, A., Oka, Y., Leptin induces proliferation of pancreatic beta cell line MIN6 through activation of mitogen-activated protein kinase (1997) Biochem. Biophys. Res. Commun., 241, pp. 765-768 
504 |a Takahashi, Y., Okimura, Y., Mizuno, I., Iida, K., Takahashi, T., Kaji, H., Abe, H., Chihara, K., Leptin induces mitogen-activated protein kinase-dependent proliferation of C3H10T1/2 cells (1997) J. Biol. Chem., 272, pp. 12897-12900 
504 |a Shah, O.J., Anthony, J.C., Kimball, S.R., Jefferson, L.S., 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle (2000) Am. J. Physiol. Endocrinol. Metab., 279, pp. E715-E729 
504 |a Pullen, N., Dennis, P.B., Andjelkovic, M., Dufner, A., Kozma, S.C., Hemmings, B.A., Thomas, G., Phosphorylation and activation of p70s6k by PDK1 (1998) Science, 279, pp. 707-710 
504 |a Shahbazian, D., Roux, P.P., Mieulet, V., Cohen, M.S., Raught, B., Taunton, J., Hershey, J.W., Sonenberg, N., The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity (2006) EMBO J., 25, pp. 2781-2791 
504 |a Lepercq, J., Cauzac, M., Lahlou, N., Timsit, J., Girard, J., Auwerx, J., Hauguel-De, M.S., Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin (1998) Diabetes, 47, pp. 847-850 
504 |a Challier, J., Galtier, M., Bintein, T., Cortez, A., Lepercq, J., Hauguel-De, M.S., Placental leptin receptor isoforms in normal and pathological pregnancies (2003) Placenta, 24, pp. 92-99 
504 |a 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 
504 |a Iwaniec, U.T., Boghossian, S., Lapke, P.D., Turner, R.T., Kalra, S.P., Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice (2007) Peptides, 28, pp. 1012-1019 
504 |a Martin-Romero, C., Santos-Alvarez, J., Goberna, R., Sanchez-Margalet, V., Human leptin enhances activation and proliferation of human circulating T lymphocytes (2000) Cell Immunol., 199, pp. 15-24 
504 |a Santos-Alvarez, J., Goberna, R., Sanchez-Margalet, V., Human leptin stimulates proliferation and activation of human circulating monocytes (1999) Cell Immunol., 194, pp. 6-11 
504 |a Steppan, C.M., Crawford, D.T., Chidsey-Frink, K.L., Ke, H., Swick, A.G., Leptin is a potent stimulator of bone growth in ob/ob mice (2000) Regul. Pept., 92, pp. 73-78 
504 |a Bifulco, G., Di, C.C., Caruso, M., Oriente, F., Di Spiezio, S.A., Formisano, P., Beguinot, F., Nappi, C., Glucose regulates insulin mitogenic effect by modulating SHP-2 activation and localization in JAr cells (2002) J. Biol. Chem., 277, pp. 24306-24314 
504 |a Boileau, P., Cauzac, M., Pereira, M.A., Girard, J., Hauguel-De, M.S., Dissociation between insulin-mediated signaling pathways and biological effects in placental cells: role of protein kinase B and MAPK phosphorylation (2001) Endocrinology, 142, pp. 3974-3979 
504 |a Diggle, T.A., Moule, S.K., Avison, M.B., Flynn, A., Foulstone, E.J., Proud, C.G., Denton, R.M., Both rapamycin-sensitive and -insensitive pathways are involved in the phosphorylation of the initiation factor-4E-binding protein (4E-BP1) in response to insulin in rat epididymal fat-cells (1996) Biochem. J., 316, pp. 447-453 
504 |a Smith, J.A., Poteet-Smith, C.E., Malarkey, K., Sturgill, T.W., Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo (1999) J. Biol. Chem., 274, pp. 2893-2898 
504 |a Chung, J., Grammer, T.C., Lemon, K.P., Kazlauskas, A., Blenis, J., PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase (1994) Nature, 370, pp. 71-75 
504 |a Li, H.L., Davis, W., Pure, E., Suboptimal cross-linking of antigen receptor induces Syk-dependent activation of p70S6 kinase through protein kinase C and phosphoinositol 3-kinase (1999) J. Biol. Chem., 274, pp. 9812-9820 
504 |a Zhang, Y., Dong, Z., Nomura, M., Zhong, S., Chen, N., Bode, A.M., Dong, Z., Signal transduction pathways involved in phosphorylation and activation of p70S6K following exposure to UVA irradiation (2001) J. Biol. Chem., 276, pp. 20913-20923 
504 |a Vanhaesebroeck, B., Leevers, S.J., Panayotou, G., Waterfield, M.D., Phosphoinositide 3-kinases: a conserved family of signal transducers (1997) Trends Biochem. Sci., 22, pp. 267-272 
504 |a Yung, H.W., Calabrese, S., Hynx, D., Hemmings, B.A., Cetin, I., Charnock-Jones, D.S., Burton, G.J., Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction (2008) Am. J. Pathol., 173, pp. 451-462 
520 3 |a Leptin, the LEP gene product, is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy. Thus, we have recently described the antiapoptotic and trophic effect of leptin on choriocarcinoma cell line JEG-3, stimulating DNA and protein synthesis. We have also demonstrated the presence of leptin receptor and leptin signaling in normal human trophoblastic cells, activating JAK-STAT, PI3K and MAPK pathways. In the present work we have employed dominant negative forms of MAPK and PKB constructs to find out the signaling pathways that specifically mediates the effect of leptin on protein synthesis. As previously shown, leptin stimulates protein synthesis as assessed by 3 H-leucine incorporation. However, both dominant negative forms of MAPK and PKB inhibited protein synthesis in JEG-3 choriocarcinoma cells. The inhibition of PKB and MAPK activity by transfection with the dominant negative kinases prevented the leptin stimulation of p70 S6K, which is known to be an important kinase in the regulation of protein synthesis. Moreover, leptin stimulation of phosphorylation of EIF4EBP1 and EIF4E, which allows the initiation of translation was also prevented by MAPK and PI3K dominant negative constructs. Therefore, these results demonstrate that both PI3K and MAPK are necessary to observe the effect of leptin signaling that mediates protein synthesis in choriocarcinoma cells JEG-3. © 2010 Elsevier Inc. All rights reserved.  |l eng 
536 |a Detalles de la financiación: Instituto de Salud Carlos III, PS09/00119, ISCIII CM07/00025 
536 |a Detalles de la financiación: This work was supported by a Grant from the Instituto de Salud Carlos III (ISCIII PS09/00119). Antonio Pérez-Pérez is a research fellow supported by the Instituto de Salud Carlos III (Contrato Post-formación especializada, Río Hortega), ISCIII CM07/00025, Spain. 
593 |a Department of Clinical Biochemistry, Virgen Macarena University Hospital, University of Seville, Spain 
593 |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina 
690 1 0 |a LEPTIN 
690 1 0 |a PROTEIN SYNTHESIS 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a TRANSLATION 
690 1 0 |a DNA 
690 1 0 |a INITIATION FACTOR 4E 
690 1 0 |a INITIATION FACTOR 4E BINDING PROTEIN 1 
690 1 0 |a JANUS KINASE 
690 1 0 |a LEPTIN 
690 1 0 |a LEPTIN RECEPTOR 
690 1 0 |a LEUCINE 
690 1 0 |a MITOGEN ACTIVATED PROTEIN KINASE 
690 1 0 |a PHOSPHATIDYLINOSITOL 3 KINASE 
690 1 0 |a PROTEIN KINASE B 
690 1 0 |a S6 KINASE 
690 1 0 |a STAT PROTEIN 
690 1 0 |a TRITIUM 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a AUTOCRINE EFFECT 
690 1 0 |a CELL GROWTH 
690 1 0 |a CHORIOCARCINOMA 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DNA SYNTHESIS 
690 1 0 |a ENZYME ACTIVATION 
690 1 0 |a ENZYME ACTIVITY 
690 1 0 |a ENZYME INHIBITION 
690 1 0 |a GENETIC TRANSFECTION 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a PREGNANCY 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN PHOSPHORYLATION 
690 1 0 |a PROTEIN SYNTHESIS 
690 1 0 |a PROTEIN SYNTHESIS INHIBITION 
690 1 0 |a PROTEIN SYNTHESIS REGULATION 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a TRANSLATION INITIATION 
690 1 0 |a TROPHOBLAST 
690 1 0 |a 1-PHOSPHATIDYLINOSITOL 3-KINASE 
690 1 0 |a ADAPTOR PROTEINS, SIGNAL TRANSDUCING 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a EUKARYOTIC INITIATION FACTOR-4E 
690 1 0 |a FEMALE 
690 1 0 |a HUMANS 
690 1 0 |a LEPTIN 
690 1 0 |a MAP KINASE SIGNALING SYSTEM 
690 1 0 |a MITOGEN-ACTIVATED PROTEIN KINASE KINASES 
690 1 0 |a PHOSPHOPROTEINS 
690 1 0 |a PHOSPHORYLATION 
690 1 0 |a PREGNANCY 
690 1 0 |a PROTEIN BIOSYNTHESIS 
690 1 0 |a PROTO-ONCOGENE PROTEINS C-AKT 
690 1 0 |a RIBOSOMAL PROTEIN S6 KINASES, 70-KDA 
690 1 0 |a TROPHOBLASTS 
650 1 7 |2 spines  |a PLACENTA 
700 1 |a Gambino, Y. 
700 1 |a Maymó, J. 
700 1 |a Goberna, R. 
700 1 |a Fabiani, F. 
700 1 |a Varone, C. 
700 1 |a Sánchez-Margalet, V. 
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