Mechanisms of leptin action on placental cell survival

TORO, AYELÉN R; IBARBALZ, FEDERICO; MAYMÓ, JULIETA; PEREZ PEREZ, ANTONIO; CALVO, JUAN CARLOS; SÁNCHEZ MARGALET, VICTOR; VARONE, CECILIA

Sevilla

Congreso; XXXV Congreso de la Sociedad Española de Bioquímica y Biología Molecular; 2012

SEBBM

Fetal-maternal dialogue during implantation involves multiple regulators such as leptin. This 16KD protein plays diverse roles in placental growth and survival. Previous results from our group demonstrated that leptin increases cell proliferation and survival in JEG-3 and BeWo cells. We also demonstrated that leptin expression is tightly regulated by different placental regulators. Objectives: The aim of the present work is to study the mechanisms involved in leptin rol on placental apoptosis. Methods: BeWo and Swan cells, and human term placental explants were used. Western blot analyses were carried out to detect leptin, caspase 3, Bcl-2, Bax and p53 expression. Transfection assays with reporter constructs were used to determine leptin effect on different transduction pathways Results: Leptin treatment diminished the proteolysis of caspase-3 in a dose dependent manner. Moreover the diminution in endogenous leptin by treatment with an antisense oligonucleotide (2-4 μM) increases cellular apoptosis measured by caspase-3 activation. Bcl-2 and Bax levels were determined after leptin treatment and the relationship between them calculated. Leptin enhanced Bcl2/Bax relation. On the other hand leptin diminished the expression of a reporter plasmid containing Bax promoter. The expression of the key cell cycle regulator p53 was also determined. Leptin diminished p53 protein level dose dependently. Conclusions: All these results reinforce the notion of leptin as a placental cytokine with the function of promoting survival of placental cells.