Leptin promotes cell proliferation and survival of trophoblastic cells
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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paper:paper_00063363_v76_n2_p203_Magarinos2023-06-08T14:31:07Z Leptin promotes cell proliferation and survival of trophoblastic cells Kotler, Mónica Lidia Calvo, Juan Carlos Varone, Cecilia Laura 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v76_n2_p203_Magarinos 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) |
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 Kotler, Mónica Lidia Calvo, Juan Carlos Varone, Cecilia Laura 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. |
author |
Kotler, Mónica Lidia Calvo, Juan Carlos Varone, Cecilia Laura |
author_facet |
Kotler, Mónica Lidia Calvo, Juan Carlos Varone, Cecilia Laura |
author_sort |
Kotler, Mónica Lidia |
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 |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v76_n2_p203_Magarinos http://hdl.handle.net/20.500.12110/paper_00063363_v76_n2_p203_Magarinos |
work_keys_str_mv |
AT kotlermonicalidia leptinpromotescellproliferationandsurvivaloftrophoblasticcells AT calvojuancarlos leptinpromotescellproliferationandsurvivaloftrophoblasticcells AT varonececilialaura leptinpromotescellproliferationandsurvivaloftrophoblasticcells |
_version_ |
1768544252958081024 |