INVESTIGADORES
SZPILBARG Natalia
congresos y reuniones científicas
Título:
EFFECT OF INTERMITTENT HYPOXIA ON CAVEOLIN-1 EXPRESSION AND ITS ASSOCIATION WITH AQUAPORIN-3 IN VILLOUS TROPHOBLASTS
Autor/es:
SZPILBARG, NATALIA; MEDINA, YOLLYSETH; MASKIN BERNARDO; SEHAYIAN ABRIL; CASTRO-PARODI MAURICIO; DAMIANO ALICIA ERMELINDA
Lugar:
Ciudad de Buenos Aires
Reunión:
Congreso; International Federation of Placenta Associations 2019 meeting and 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta; 2019
Institución organizadora:
IFPA-SLIMP
Resumen:
Objectives:To evaluate the effect of oxygen tensionfluctuations on cav-eolae/caveolin-1 (Cav-1) expression and lipid membrane composition invillous trophoblast, and to analyze the association between aquaporin-3(AQP3) and Cav-1.Methods:This study was approved by the Ethics Committee of the Hos-pital Nacional Prof. Dr. Posadas. Normal placental explants were culturedin normoxia and hypoxia/reoxygenation. Cav-1 expression was analyzedby RT-PCR and Western blot. Total lipids from apical (MVM) and basalmembrane (BM) vesicles were extracted, total phospholipid amount wasdetermined. Individual phospholipids species were separated by thin-layer chromatography and quantified. Cholesterol amount was alsodetermined.In silicoanalysis of putative Cav-1 binding motifs in AQP3protein was performed. Cav-1 and AQP3 association was investigated bydouble immunofluorescence and by immunoprecipitation experiments,immobilizing Cav-1 antibody and specifically detecting AQP3.Results:Cav-1 protein and mRNA expression decreased in hypoxia/reox-ygenation. Total phospholipid amount increased after hypoxia/reoxyge-nation treatment in MVM at the expense of an increase in sphyngomyelin,while cholesterol amount did not change. Membranefluidity of MVM also decreased. The analysis of the primary structure of AQP3 identified a pu-tative Cav-1 binding site containing the region between the third andfourth transmembrane domains. The presence of AQP3/Cav-1 complexwas detected by immunoprecipitation with Cav-1 antibody and confirmedby double immunofluorescence. Conclusion: Protein/protein interactions and regulated incorporation intoplasma membrane microdomains may modulate AQPs. Our findings suggest that fluctuations in oxygen tension may alter lipid membrane composition of the trophoblasts, disturbing the ability of sphyngomyelinand cholesterol to assembly into caveolae and reducing Cav-1 expression. Since AQP3 has a role in trophoblast apoptosis, these changes may create an unfavorable environment for AQP3 insertion in the MVM affecting villous trophoblast differentiation and turnover, which may be involved in the development of preeclampsia.