Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway

J MAYMÓ; A PÉREZ PÉREZ; JC CALVO; V SÁNCHEZ MARGALET; C VARONE

Los Cocos, Córdoba, Argentina

Congreso; III Simposio Latinoamericano: Interacción Materno-fetal y Placenta; 2007

Sociedad Latinoamericano: Interacción Materno-fetal y Placenta

Leptin, the peripheral signal produced by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may have a role as an autocrine hormone. Recently, we have demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the signal transduction pathways that mediate the antiapoptotic effect of leptin in placenta. Methods: JEG-3 cells, cultured under standard conditions, as well as human placenta explants were used. Western blot analyses were carried out to detect the phosphorylated form of proteins involved in mayor signalling pathways. The early phase of apoptosis, triggered by the lack of serum, was assayed by flow cytometric detection of phosphatidyl serine translocation using FITC-labelled Annexin V and by western blot of caspase-3 fragmentation. Results: We have found that leptin stimulates JAK-STAT pathway by promoting JAK2 and STAT3 tyrosine phosphorylation. We have also demonstrated the activation of MAPK pathway by studying phosphorylation of MEK and MAPK (Erk1/2). PI3K pathway is also triggered by leptin stimulation as assessed by the study of PKB phosphorylation. These signaling pathways were confirmed in explants obtained from placenta of healthy donors. The effect of leptin on JEG-3 survival was completely reversed by blocking p42/44 MAPK activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using Wortmannin. Conclusions: All these findings suggest that the leptin antiapoptotic effect in JEG-3 cells is mediated by the p42/44 MAPK pathway.