Selective Fluidization of Synaptosomal Plasma Membrane Vesicles by 17β-Estradiol

Abstract

Estrogens are effective neuroprotectants in vivo and in vitro. To obtain a better insight into the molecular mechanisms of action of neuroprotection by 17β-estradiol (E2), we examined the differential effects of E2 on the fluidity of synaptosomal plasma membrane vesicles (SPMV) isolated from rat cerebral cortex. Intramolecular excimerization of 1,3-di(1-pyrenyl)-propane (Py-3-Py) was used to investigate the effects of E2 on the bulk and annular lateral diffusion of the SPMV. In addition, we examined the effects of E2 on the rotational diffusion of individual leaflet of SPMV exploiting selective quenching of outer monolayer 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence by trinitrophenyl groups. The Förster distance R 0 value for the tryptophan-Py-3-Py donor-acceptor pair was 26.9 Å. E2 increased the lateral mobility of both bulk and annular lipids in SPMV in a dose-dependent manner, but a larger effect on bulk lipids was observed. Although E2 decreased the anisotropy of DPH in SPMV, E2 had a greater fluidizing effect on the outer leaflet compared to the inner leaflet. These results suggest that E2 selectively fluidizes the more fluid regions within SPMV. It is highly probable that E2 mostly fluidizes the bulk lipids, away from either annular lipids or lipid rafts, in the outer leaflet of SPMV. This selective fluidization may be one of the nongenomic mechanisms of neuroprotection by E2.