Leptin stimulates protein synthesis activating translation machinery in human trophoblastic cells

PÉREZ PÉREZ A; MAYMÓ J; GAMBINO Y; DUEÑAS JL; VARONE C; SÁNCHEZ MARGALET V

BIOLOGY OF REPRODUCTION

SOC STUDY REPRODUCTION

Año: 2009 vol. 81 p. 826 - 832

0006-3363

Leptin was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it may work as an autocrine hormone, mediating angiogenesis, growth and immunomodulation. Leptin receptor (LEPR, also known as Ob-R) shows sequence homology to members of the class I cytokine receptor (gp130) superfamily. In fact, leptin may function as a proinflammatory cytokine. We have previously found that leptin is a trophic and mitogenic factor for trophoblastic cells. In order to further investigate the mechanism by which leptin stimulates cell growth in JEG-3 cells and trophoblastic cells, we studied phosphorylation state of different proteins of the initiation stage of translation, and total protein synthesis by [3H]leucine incorporation in JEG-3 cells. We have found that leptin dose-dependently stimulates the phosphorylation and activation of the translation initiation factor EIF4E as well as the phosphorylation of the EIF4E binding protein EIF4EBP1 (PHAS-I), which releases EIF4E to form active complexes. Moreover, leptin dose-dependently stimulates protein synthesis, and this effect can be partially prevented by blocking MAPK and PIK3 pathways. In conclusion, leptin stimulates protein synthesis at least in part activating the translation machinery, via the activation of MAPK and PIK3 pathways.