Leptin promotes cell proliferation and survival of trophoblastic cells

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Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we s...

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Autores principales: Magariños, M.P., Sánchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2007
Materias:
Apoptosis
Growth factors
Leptin
Mechanisms of hormone action
Placenta
caspase 3
fluorescein isothiocyanate
leptin
lipocortin 5
propidium iodide
thymidine
tritium
apoptosis
article
cell proliferation
cell survival
controlled study
dose response
drug mechanism
human
human cell
placenta function
priority journal
trophoblast
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00063363_v76_n2_p203_Magarinos
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paperaa:paper_00063363_v76_n2_p203_Magarinos
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spelling paperaa:paper_00063363_v76_n2_p203_Magarinos2023-06-12T16:41:16Z Leptin promotes cell proliferation and survival of trophoblastic cells Biol. Reprod. 2007;76(2):203-210 Magariños, M.P. Sánchez-Margalet, V. Kotler, M. Calvo, J.C. Varone, C.L. Apoptosis Growth factors Leptin Mechanisms of hormone action Placenta caspase 3 fluorescein isothiocyanate leptin lipocortin 5 propidium iodide thymidine tritium apoptosis article cell proliferation cell survival controlled study dose response drug mechanism human human cell placenta function priority journal trophoblast Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by 3H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 μM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 μM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. © 2007 by the Society for the Study of Reproduction, Inc. Fil:Kotler, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00063363_v76_n2_p203_Magarinos
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language Inglés
orig_language_str_mv eng
topic Apoptosis
Growth factors
Leptin
Mechanisms of hormone action
Placenta
caspase 3
fluorescein isothiocyanate
leptin
lipocortin 5
propidium iodide
thymidine
tritium
apoptosis
article
cell proliferation
cell survival
controlled study
dose response
drug mechanism
human
human cell
placenta function
priority journal
trophoblast
spellingShingle Apoptosis
Growth factors
Leptin
Mechanisms of hormone action
Placenta
caspase 3
fluorescein isothiocyanate
leptin
lipocortin 5
propidium iodide
thymidine
tritium
apoptosis
article
cell proliferation
cell survival
controlled study
dose response
drug mechanism
human
human cell
placenta function
priority journal
trophoblast
Magariños, M.P.
Sánchez-Margalet, V.
Kotler, M.
Calvo, J.C.
Varone, C.L.
Leptin promotes cell proliferation and survival of trophoblastic cells
topic_facet Apoptosis
Growth factors
Leptin
Mechanisms of hormone action
Placenta
caspase 3
fluorescein isothiocyanate
leptin
lipocortin 5
propidium iodide
thymidine
tritium
apoptosis
article
cell proliferation
cell survival
controlled study
dose response
drug mechanism
human
human cell
placenta function
priority journal
trophoblast
description Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by 3H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 μM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 μM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. © 2007 by the Society for the Study of Reproduction, Inc.
format Artículo
Artículo
publishedVersion
author Magariños, M.P.
Sánchez-Margalet, V.
Kotler, M.
Calvo, J.C.
Varone, C.L.
author_facet Magariños, M.P.
Sánchez-Margalet, V.
Kotler, M.
Calvo, J.C.
Varone, C.L.
author_sort Magariños, M.P.
title Leptin promotes cell proliferation and survival of trophoblastic cells
title_short Leptin promotes cell proliferation and survival of trophoblastic cells
title_full Leptin promotes cell proliferation and survival of trophoblastic cells
title_fullStr Leptin promotes cell proliferation and survival of trophoblastic cells
title_full_unstemmed Leptin promotes cell proliferation and survival of trophoblastic cells
title_sort leptin promotes cell proliferation and survival of trophoblastic cells
publishDate 2007
url http://hdl.handle.net/20.500.12110/paper_00063363_v76_n2_p203_Magarinos
work_keys_str_mv AT magarinosmp leptinpromotescellproliferationandsurvivaloftrophoblasticcells
AT sanchezmargaletv leptinpromotescellproliferationandsurvivaloftrophoblasticcells
AT kotlerm leptinpromotescellproliferationandsurvivaloftrophoblasticcells
AT calvojc leptinpromotescellproliferationandsurvivaloftrophoblasticcells
AT varonecl leptinpromotescellproliferationandsurvivaloftrophoblasticcells
_version_ 1769810154315841536

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