FK506 binding protein 52 modulated AP-1 functions in human trophoblast cells

SONIA DE LEO; MARIO GALIGNIANA; MARIA FERNANDA CAMISAY; ALEJANDRA ERLEJMAN

Puerto Varas

Congreso; International Congress of the Society for Maternal-Fetal Interaction & Placenta; 2017

Society for Maternal-Fetal Interaction & Placenta

FK506 binding protein 52 (FKBP52) is a cochaperone that influences steroid receptors function and has peptidylprolyl-isomerase (PPIase) activity. Reduced FKBP52 protein has been detected in placentas from preeclampsia (PE), also it has been suggested that c-fos is implicated in regulating invasive mechanism of trophoblast in PE as well as in placentas from normal gestations.Objective: The aim of this work was to investigate the effect of FKBP52 on the transcription factor activator protein 1 (AP-1) in trophoblast cells.Methods: BeWo were used as in vitro choriocarcinoma model. Cells were transfected with wild type FKBPs or their putative PPIase mutants, and then, stimulated by miristic-acetated phorbol ester 12-myristate 13-acetate (PMA). AP-1 signalling was evaluated by luciferase assays and Western blot, analysing endogenous c-fos expression and monitoring phophorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2)/total ERK ratio along time (90 min). Interleukin 6 (IL-6) secretion was measured by ELISA, and matrix metalloproteinase 2 (MMP-2) proteolytic activity was determined by zymography.Results: After 30 min of PMA treatment ERK1/2 acquired its maximum phosphorylation level. In the presence of FKBP52 total ERK1/2 was unaltered, but pERK1/2 / total ERK1/2 remained increased along time (P