Leptin reduces p53 levels in human placental cells

AYELÉN TORO; JULIETA L. MAYMÓ; ANTONIO PÉREZ-PÉREZ; BERNARDO MASKIN; VÍCTOR SÁNCHEZ-MARGALET; CECILIA L. VARONE

Madrid

Congreso; XXXVI Congreso de la Sociedad Española de Bioquímica y Biología Molecular; 2013

Leptin reduces p53 levels in human placental cells   Toro, Ayelén1; Maymó, Julieta1; Pérez Pérez, Antonio2; Maskin, Bernardo3; Sánchez- Margalet,  Victor2; Varone, Cecilia1.   1Departamento de Química Biológica Facultad de Ciencia Exactas y Naturales- Universidad de Buenos Aires, IQUIBICEN/CONICET, Argentina. 2Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, España. 3Hospital Nacional ?Profesor A. Posadas?, Argentina.   Fetal-maternal dialogue during implantation involves multiple regulators: adhesion molecules, proteases, hormones and citoquines such as leptin. This 16 kDa protein plays diverse roles in placental growth and survival, immunomodulation and angiogenesis. Previous results from our group evidenced that leptin increased cell proliferation and survival in JEG-3 and BeWo cells, involving probably the MAPK signaling pathway. We also found that leptin reduced caspase-3 activation. The aim of the present work is to study the mechanisms involved in leptin action on placental survival, studying p53 levels. Swan cells and human term placental explants were used. Western blot analyses were carried out to detect p53. Pharmacological inhibitors and transfection assays were used to determine different transduction pathways involved in leptin effect. Our results showed that leptin treatment diminished p53 levels in trophoblastic cells and human placental explants. Swan cells treated with LY294002 or PD98059, pharmacological inhibitors of PI3K and MAPK pathways respectively, showed no effect of leptin on p53 level. When Swan cells were transfected with an expression plasmid for a dominant negative mutant of Akt, leptin did not decrease p53 levels. Similar evidences were found in human placental explants. All together, these results revealed that leptin diminished p53 level trough PI3K/Akt and MAPK signaling, reinforcing the notion of leptin as a placental cytokine with the function of promoting survival of placental cells.