Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells
Leptin was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it may work as an autocrine hormone, mediating angiogenesis, g...
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paper:paper_00063363_v81_n5_p826_PerezPerez2023-06-08T14:31:09Z Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells Maymó, Julieta L. Gambino, Yésica Paola Varone, Cecilia Laura Leptin Leptin receptor Mechanisms of hormone action Placenta Trophoblast initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase 2 (2 amino 3 methoxyphenyl)chromone androstane derivative EIF4EBP1 protein, human flavonoid initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase phosphoprotein protein kinase inhibitor signal transducing adaptor protein wortmannin article cell growth controlled study hormone action human human cell priority journal protein binding protein phosphorylation protein synthesis translation initiation trophoblast analysis of variance cell culture cell line dose response drug effect female metabolism phosphorylation physiology placenta pregnancy protein synthesis signal transduction Western blotting 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Analysis of Variance Androstadienes Blotting, Western Cell Line Cells, Cultured Dose-Response Relationship, Drug Eukaryotic Initiation Factor-4E Female Flavonoids Humans Leptin Mitogen-Activated Protein Kinases Phosphoproteins Phosphorylation Placenta Pregnancy Protein Biosynthesis Protein Kinase Inhibitors Signal Transduction Trophoblasts Leptin was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it may work as an autocrine hormone, mediating angiogenesis, growth, and immunomodulation. Leptin receptor (LEPR, also known as Ob-R) shows sequence homology to members of the class I cytokine receptor (gp130) superfamily. In fact, leptin may function as a proinflammatory cytokine. We have previously found that leptin is a trophic and mitogenic factor for trophoblastic cells. In order to further investigate the mechanism by which leptin stimulates cell growth in JEG-3 cells and trophoblastic cells, we studied the phosphorylation state of different proteins of the initiation stage of translation and the total protein synthesis by [3H]leucine incorporation in JEG-3 cells. We have found that leptin dose-dependently stimulates the phosphorylation and activation of the translation initiation factor EIF4E as well as the phosphorylation of the EIF4E binding protein EIF4EBP1 (PHAS-I), which releases EIF4E to form active complexes. Moreover, leptin dose-dependently stimulates protein synthesis, and this effect can be partially prevented by blocking mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PIK3) pathways. In conclusion, leptin stimulates protein synthesis, at least in part activating the translation machinery, via the activation of MAPK and PIK3 pathways. © 2009 by the Society for the Study of Reproduction, Inc. Fil:Julieta Maymo, Y. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gambino, É. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varone, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v81_n5_p826_PerezPerez http://hdl.handle.net/20.500.12110/paper_00063363_v81_n5_p826_PerezPerez |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Leptin Leptin receptor Mechanisms of hormone action Placenta Trophoblast initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase 2 (2 amino 3 methoxyphenyl)chromone androstane derivative EIF4EBP1 protein, human flavonoid initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase phosphoprotein protein kinase inhibitor signal transducing adaptor protein wortmannin article cell growth controlled study hormone action human human cell priority journal protein binding protein phosphorylation protein synthesis translation initiation trophoblast analysis of variance cell culture cell line dose response drug effect female metabolism phosphorylation physiology placenta pregnancy protein synthesis signal transduction Western blotting 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Analysis of Variance Androstadienes Blotting, Western Cell Line Cells, Cultured Dose-Response Relationship, Drug Eukaryotic Initiation Factor-4E Female Flavonoids Humans Leptin Mitogen-Activated Protein Kinases Phosphoproteins Phosphorylation Placenta Pregnancy Protein Biosynthesis Protein Kinase Inhibitors Signal Transduction Trophoblasts |
spellingShingle |
Leptin Leptin receptor Mechanisms of hormone action Placenta Trophoblast initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase 2 (2 amino 3 methoxyphenyl)chromone androstane derivative EIF4EBP1 protein, human flavonoid initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase phosphoprotein protein kinase inhibitor signal transducing adaptor protein wortmannin article cell growth controlled study hormone action human human cell priority journal protein binding protein phosphorylation protein synthesis translation initiation trophoblast analysis of variance cell culture cell line dose response drug effect female metabolism phosphorylation physiology placenta pregnancy protein synthesis signal transduction Western blotting 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Analysis of Variance Androstadienes Blotting, Western Cell Line Cells, Cultured Dose-Response Relationship, Drug Eukaryotic Initiation Factor-4E Female Flavonoids Humans Leptin Mitogen-Activated Protein Kinases Phosphoproteins Phosphorylation Placenta Pregnancy Protein Biosynthesis Protein Kinase Inhibitors Signal Transduction Trophoblasts Maymó, Julieta L. Gambino, Yésica Paola Varone, Cecilia Laura Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
topic_facet |
Leptin Leptin receptor Mechanisms of hormone action Placenta Trophoblast initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase 2 (2 amino 3 methoxyphenyl)chromone androstane derivative EIF4EBP1 protein, human flavonoid initiation factor 4E leptin mitogen activated protein kinase phosphatidylinositol 3 kinase phosphoprotein protein kinase inhibitor signal transducing adaptor protein wortmannin article cell growth controlled study hormone action human human cell priority journal protein binding protein phosphorylation protein synthesis translation initiation trophoblast analysis of variance cell culture cell line dose response drug effect female metabolism phosphorylation physiology placenta pregnancy protein synthesis signal transduction Western blotting 1-Phosphatidylinositol 3-Kinase Adaptor Proteins, Signal Transducing Analysis of Variance Androstadienes Blotting, Western Cell Line Cells, Cultured Dose-Response Relationship, Drug Eukaryotic Initiation Factor-4E Female Flavonoids Humans Leptin Mitogen-Activated Protein Kinases Phosphoproteins Phosphorylation Placenta Pregnancy Protein Biosynthesis Protein Kinase Inhibitors Signal Transduction Trophoblasts |
description |
Leptin was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it may work as an autocrine hormone, mediating angiogenesis, growth, and immunomodulation. Leptin receptor (LEPR, also known as Ob-R) shows sequence homology to members of the class I cytokine receptor (gp130) superfamily. In fact, leptin may function as a proinflammatory cytokine. We have previously found that leptin is a trophic and mitogenic factor for trophoblastic cells. In order to further investigate the mechanism by which leptin stimulates cell growth in JEG-3 cells and trophoblastic cells, we studied the phosphorylation state of different proteins of the initiation stage of translation and the total protein synthesis by [3H]leucine incorporation in JEG-3 cells. We have found that leptin dose-dependently stimulates the phosphorylation and activation of the translation initiation factor EIF4E as well as the phosphorylation of the EIF4E binding protein EIF4EBP1 (PHAS-I), which releases EIF4E to form active complexes. Moreover, leptin dose-dependently stimulates protein synthesis, and this effect can be partially prevented by blocking mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PIK3) pathways. In conclusion, leptin stimulates protein synthesis, at least in part activating the translation machinery, via the activation of MAPK and PIK3 pathways. © 2009 by the Society for the Study of Reproduction, Inc. |
author |
Maymó, Julieta L. Gambino, Yésica Paola Varone, Cecilia Laura |
author_facet |
Maymó, Julieta L. Gambino, Yésica Paola Varone, Cecilia Laura |
author_sort |
Maymó, Julieta L. |
title |
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
title_short |
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
title_full |
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
title_fullStr |
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
title_full_unstemmed |
Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
title_sort |
leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells |
publishDate |
2009 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v81_n5_p826_PerezPerez http://hdl.handle.net/20.500.12110/paper_00063363_v81_n5_p826_PerezPerez |
work_keys_str_mv |
AT maymojulietal leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells AT gambinoyesicapaola leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells AT varonececilialaura leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells |
_version_ |
1768541919337512960 |