Trophoblastic cell survival regulation by leptin under hypoxic condition

MALENA SCHANTON; JULIETA L. MAYMÓ; PAULA BALESTRINI; BERNARDO MASKIN; NATALY DE DIOS; RIEDEL, RODRIGO; CECILIA L. VARONE

Mar del Plata

Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica; 2018

Trophoblastic cell survival regulation by leptin under hypoxic conditionNataly de Dios1, Paula Balestrini2, Malena Schanton1, Rodrigo Riedel1, Bernardo Maskin3, Julieta Maymó1 and Cecilia Varone11 Departamento de Química Biológica FCEN-UBA. Instituto de Química Biológica FCEN, IQUIBICEN, CONICET2 Instituto de Biología y Medicina Experimental IByME3 Hospital Nacional Profesor Alejandro PosadasLeptin is a pleiotropic hormone produced by the placenta where it plays important functions. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the mechanisms that mediate the effect of leptin in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes HIF-1 transcription factor. For this study we use Swan-71 cells, a first trimester trophoblastic human cell line, cultured under standard conditions, as well as human term placenta explants. Swan-71 cells and placental explants were treated with CoCl2 (50, 100 and 250 µM) to induce cellular stress and with or without 100 ng/ml of recombinant leptin. The expression of HIF-1α, p53, Ki67 was determinate by Western blot or immunofluorescence (IF). All procedures were approved by ethical review committee at the Alejandro Posadas National Hospital. The role of leptin on proliferation and survival in Swan-71 cells treated with CoCl2 (50, 100 and 250 µM) was also determined. The expression of the proliferation marker Ki67 was determined by IF and the viability was assessed by the MTT assay.In order to prove CoCl2 effect, we studied HIF-1α expression and we confirmed that the treatment with 100 µM of CoCl2 induced its expression in a time and dose dependent way () and leptin seems to reduced HIF-1α levels. Next we evaluated p53 expression on trophoblastic cells treated with CoCl2 and found that p53 expression is increased by CoCl2 treatment. In these conditions leptin reduced the expression of p53. On the other hand, leptin increases cell proliferation and HIF-1 stabilization blocked this effect. These findings suggest that leptin is capable to protect placental cells under hypoxia conditions. Key words: Placenta, apoptosis, hypoxia, leptin