IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ANTIAPOPTOTIC EFFECTS OF LEPTIN ON TROPHOBLASTS
Autor/es:
AYELÉN TORO; MALENA SCHANTON; JULIETA MAYMÓ; ANTONIO PÉREZ-PÉREZ; BERNARDO MASKIN; VICTOR SÁNCHEZ MARGALET; CECILIA VARONE
Lugar:
Mar del Plata
Reunión:
Congreso; V Simposio Latinoamericano: Interacción Materno-fetal y Placenta (SLIMP); 2015
Institución organizadora:
SLIMP
Resumen:
Leptin produced by the placenta has many roles as an autocrine hormone.We have previously demonstrated that leptin promotes proliferation andsurvival of trophoblast cells. In the present work, we aimed to study themechanisms that mediate the antiapoptotic effect of leptin in the placenta.Methods: BeWo and Swan cells, cultured under standard conditions, aswell as human placental explants were used. Western blot, qRT-PCR andtransfection assays with reporter constructs and expression vectors werecarried out. All the procedures were approved by the ethical reviewcommittee at the Posadas National Hospital (Buenos Aires, Argentina).Results: Recombinant human leptin added to the BeWo cell line and humanplacental explants showed a decrease in Caspase-3 activation in adose- dependent manner. Moreover, inhibition of endogenous leptinexpression with 2 mM of an antisense oligonucleotide reversed Caspase-3diminution. We also found that the cleavage of Poly [ADP-ribose] polymerase-1 (PARP-1) was diminished in the presence of leptin. Placentalexplants cultured in the absence of serum in the culture media increasedthe apoptotic cleavage of DNA and this effect was prevented by the additionof 100 ng leptin/ml. We found that under serum deprivation conditions,leptin increased the anti-apoptotic Bcl-2 protein expression anddownregulated the pro-apoptotic Bax and Bid protein expression in Swan-71 cells and placental explants. In both models, leptin augmented the Bcl-2/Bax ratio. Moreover, we demonstrated that p53, one of the key cell cyclesignalingproteins, is downregulated in the presence of leptin under serumdeprivation. Leptin also reduced the phosphorylation of Ser-46 p53, whichplays a pivotal role in the apoptotic signaling by p53 and augments thelevels of Mdm2 protein, a regulator of p53 half-life. Furthermore, leptinantiapoptotic effect and p53 regulation by leptin involved MAPK and PI3Ksignaling pathways.Conclusions: These results improve the understanding of leptin functionduring pregnancy and further support the importance of leptin in pregnancy.