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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Autores principales: Pérez-Pérez, A., Julieta Maymo, Y., Gambino, É., Dueñas, J.L., Goberna, R., Varone, C., Sánchez-Margalet, V.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00063363_v81_n5_p826_PerezPerez
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spelling todo:paper_00063363_v81_n5_p826_PerezPerez2023-10-03T14:04:58Z Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells Pérez-Pérez, A. Julieta Maymo, Y. Gambino, É. Dueñas, J.L. Goberna, R. Varone, C. Sánchez-Margalet, V. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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
Pérez-Pérez, A.
Julieta Maymo, Y.
Gambino, É.
Dueñas, J.L.
Goberna, R.
Varone, C.
Sánchez-Margalet, V.
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.
format JOUR
author Pérez-Pérez, A.
Julieta Maymo, Y.
Gambino, É.
Dueñas, J.L.
Goberna, R.
Varone, C.
Sánchez-Margalet, V.
author_facet Pérez-Pérez, A.
Julieta Maymo, Y.
Gambino, É.
Dueñas, J.L.
Goberna, R.
Varone, C.
Sánchez-Margalet, V.
author_sort Pérez-Pérez, A.
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
url http://hdl.handle.net/20.500.12110/paper_00063363_v81_n5_p826_PerezPerez
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AT duenasjl leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells
AT gobernar leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells
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AT sanchezmargaletv leptinstimulatesproteinsynthesisactivatingtranslationmachineryinhumantrophoblasticcells
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