Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux

<p>Abstract</p> <p>Background</p> <p>Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT).</p> <p>Results</p> <p>In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E₂), estrone (E₁), and estriol (E₃)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E₂-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca²⁺-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E₂-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10^-9M E₂treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E₁and E₃can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane.</p> <p>Conclusion</p> <p>Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.</p

Ultrasmall Gold Nanoparticles Anchored to Graphene and Enhanced Photothermal Effects by Laser Irradiation of Gold Nanostructures in Graphene Oxide Solutions

In this work we demonstrate the coupling of the photothermal effects of gold nanostructures of controlled size and shape with graphene oxide nanosheets dispersed in water. The enhanced photothermal effects can be tuned by controlling the shape and size of the gold nanostructures, which result in a remarkable increase in the heating efficiency of the laser-induced size reduction of gold nanostructures. The Raman spectra of the Au–graphene nanosheets provide direct evidence for the presence of more structural defects in the graphene lattice induced by laser irradiation of graphene oxide nanosheets in the presence of Au nanostructures. The large surface areas of the laser-reduced graphene oxide nanosheets with multiple defect sites and vacancies provide efficient nucleation sites for the ultrasmall gold nanoparticles with diameters of 2–4 nm to be anchored to the graphene surface. This defect filling mechanism decreases the mobility of the ultrasmall gold nanoparticles and, thus, stabilizes the particles against the Ostwald ripening process, which leads to a broad size distribution of the laser-size-reduced gold nanoparticles. The Au nanostructures/graphene oxide solutions and the ultrasmall gold–graphene nanocomposites are proposed as promising materials for photothermal therapy and for the efficient conversion of solar energy into usable heat for a variety of thermal, thermochemical, and thermomechanical applications