INVESTIGADORES
MARTINEZ Nora Alicia
congresos y reuniones científicas
Título:
HYPOXIA INDUCIBLE FACTOR-1 ALPHA (HIF-1α) UPREGULATES AQP4 EXPRESSION IN HUMAN PLACENTAS
Autor/es:
SZPILBARG N.; DI PAOLA M; ETCHEVERRY T; CASTRO PARODI M; MARTÍNEZ N.; FARINA M; DAMIANO A
Lugar:
Buenos Aires
Reunión:
Congreso; REUNION CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017
Resumen:
In preeclamptic placentas (PE), aberrations in the remodeling of the spiral arteries lead to fluctuations in O2 tension, resulting in an ischemia-reperfusion (hypoxia/reoxygenation [H/R])-type injury. Previous reports show that HIF-1α is significantly overexpressed in PE due to a proteasome dysfunction, contributing to the dysregulation of numerous genes, including syncytiotrophoblast transporters such as aquaporins (AQPs). In-silico analysis showed 3 putative binding sites for HIF-1α in AQP4 promotor region. Recently, we described that both CoCl2 (a HIF-1α inducer) and hypoxia (H) treatment enhanced HIF-1α and AQP4 expression in placental explants and both returned to basal levels after reoxygenation. However, despite HIF-1α overexpression and the proteasome dysfunction, AQP4 is decreased in PE. Our aim is to study AQP4 expression and protein degradation pathways in placenta. Our hypothesis is that AQP4 mRNA expression is increased in H and in PE via HIF-1α and that protein degradation occurs via the lysosome pathway.This study was approved by an ethical committee. We performed AQP4 semiquantitative RT-PCR in normal and PE placental explants cultured in different O2 conditions or in the presence of CoCl2 and evaluated AQP4 expression. Incubations with MG-132 or NH4Cl, proteasome and lysosome inhibitors respectively, were also performed. We found that AQP4 mRNA increased in H, CoCl2 and PE (2.3-fold, 1.5-fold, 5-fold; n=4, p