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Abstract:

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.

Registro:

Documento: Artículo
Título:Leptin promotes cell proliferation and survival of trophoblastic cells
Autor:Magariños, M.P.; Sánchez-Margalet, V.; Kotler, M.; Calvo, J.C.; Varone, C.L.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Departamento de Bioquímica Médica Y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain
Instituto de Biología Y Medicina Experimental (IBYME), 1428 Buenos Aires, Argentina
Departamento de Química Biológica, Ciudad Universitaria, Pabellón 2, (1428) Buenos Aires, Argentina
Palabras clave: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
Año:2007
Volumen:76
Número:2
Página de inicio:203
Página de fin:210
DOI: http://dx.doi.org/10.1095/biolreprod.106.051391
Título revista:Biology of Reproduction
Título revista abreviado:Biol. Reprod.
ISSN:00063363
CODEN:BIREB
CAS:caspase 3, 169592-56-7; fluorescein isothiocyanate, 25168-13-2, 27072-45-3, 3326-32-7; lipocortin 5, 111237-10-6; propidium iodide, 25535-16-4; thymidine, 50-89-5; tritium, 10028-17-8
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00063363_v76_n2_p203_Magarinos.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v76_n2_p203_Magarinos

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Citas:

---------- APA ----------
Magariños, M.P., Sánchez-Margalet, V., Kotler, M., Calvo, J.C. & Varone, C.L. (2007) . Leptin promotes cell proliferation and survival of trophoblastic cells. Biology of Reproduction, 76(2), 203-210.
http://dx.doi.org/10.1095/biolreprod.106.051391
---------- CHICAGO ----------
Magariños, M.P., Sánchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L. "Leptin promotes cell proliferation and survival of trophoblastic cells" . Biology of Reproduction 76, no. 2 (2007) : 203-210.
http://dx.doi.org/10.1095/biolreprod.106.051391
---------- MLA ----------
Magariños, M.P., Sánchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L. "Leptin promotes cell proliferation and survival of trophoblastic cells" . Biology of Reproduction, vol. 76, no. 2, 2007, pp. 203-210.
http://dx.doi.org/10.1095/biolreprod.106.051391
---------- VANCOUVER ----------
Magariños, M.P., Sánchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L. Leptin promotes cell proliferation and survival of trophoblastic cells. Biol. Reprod. 2007;76(2):203-210.
http://dx.doi.org/10.1095/biolreprod.106.051391