The unfavourable lipid environment reduced caveolin-1 expression in apical membranes from human preeclamptic placentas

LEVI LORENA; CASTRO-PARODI MAURICIO; MARTÍNEZ NORA; PIEHL LIDIA; RRUBÍN DE CELIS EMILIO; HERLAX VANESA; MATE SABINA; FARINA MARIANA; DAMIANO ALICIA

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 1858 p. 2171 - 2180

0005-2736

Normal syncyalization process is associated with a reduction in the number of caveolas, and a decreased expression of caveolin-1 (Cav-1). Furthermore, differentiation of syncytiotrophoblast affects the phospholipid composition of plasma membranes. Thus, disturbances in these processes are related to pathological conditions such as preeclampsia. OBJECTIVE: To analyse the lipid composition of the apical (MVM) and the basal (BM) membranes of syncytiotrophoblast and its relationship with the expression of Cav-1 in normal and preeclamptic placentas.METHODS: Molecular expression of Cav-1 was determined in MVM and BM from normal and preeclamptic placentas and in detergent-resistant membranes (DRMs). Phospholipids were analyzed by thin layer chromatography. Cholesterol was also determined by enzymatic assay. Membrane fluidity was evaluated by electron paramagnetic resonance. Sphingomyelin (SM) molecular species were analyzed and quantified by gas-liquid chromatography and mass spectrometry.RESULTS: Cav-1 expression was significantly reduced in MVM from preeclamptic placentas. Regarding Cav-1 localization in these placentas, it was barely detectable in syncytiotrophobast but it was present in the endothelium. Accordingly with this result, Western blots also showed a significantly decrease of Cav-1 in the apical DRMs from preeclamptic placentas. Lipid composition analysis showed an increase SM in MVM from preeclamptic placentas without changes in cholesterol amount. In addition, preeclamptic MVM fluidity decreased significantly and we found an increase in C18:1 fatty acids of SM.CONCLUSIONS: Our results show that preeclamptic MVMs are more rigid than normal ones, possible due to an increment on SM content. Moreover, the increase of long and unsaturated SM molecular specie found in these vesicles may disrupt the ability of SM to assemble into lipid rafts in the luminal leaflet of the bilayer, creating an unfavorable environment for appropriated location of Cav-1.