ABSTRACT
As inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins have pleiotropic vascular-protective effects, such as anti-inflammatory and antioxidative effects. We investigated the short-term beneficial effects of statins on modulating the translocation of lipid-raft-related proteins in endothelial cells (ECs). Human umbilical vein ECs were treated with atorvastatin for 30 min or 2 h; lipid-raft proteins were isolated and examined by quantitative proteome assay. Functional classification of identified proteins in lipid rafts revealed upregulated antioxidative proteins; downregulated proteins were associated with inflammation and cell adhesion. Among proteins verified by Western blot analysis, endoplasmic reticulum protein 46 (ERp46) showed increased level in lipid rafts with atorvastatin. Further, atorvastatin inhibited the activation of membrane-bound NADPH oxidase in both untreated and angiotensin II-treated ECs, as shown by reduced reactive oxygen species production. Co-immunoprecipitation and immunofluorescence experiments revealed that atorvastatin increased the association of ERp46 and Nox2, an NADPH oxidase isoform, in lipid rafts, thereby inhibiting Nox2 assembly with its regulatory subunits, such as p47phox and p67phox. Our results reveal a novel antioxidative role of atorvastatin by promoting the membrane translocation of ERp46 and its binding with Nox2 to inhibit Nox2 activity in ECs, which may offer another insight into the pleiotropic functions of statins.
Subject(s)
Antioxidants/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Membrane Microdomains/chemistry , Proteome/metabolism , Amino Acid Sequence , Atorvastatin , Heptanoic Acids/pharmacology , Human Umbilical Vein Endothelial Cells/chemistry , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Membrane Glycoproteins/analysis , Membrane Glycoproteins/metabolism , Membrane Microdomains/metabolism , Molecular Sequence Data , NADPH Oxidase 2 , NADPH Oxidases/analysis , NADPH Oxidases/metabolism , Protein Disulfide-Isomerases/analysis , Protein Disulfide-Isomerases/metabolism , Proteins/analysis , Proteins/classification , Proteins/metabolism , Proteome/analysis , Proteome/drug effects , Pyrroles/pharmacology , Reactive Oxygen Species/analysis , Reactive Oxygen Species/metabolism , Reproducibility of ResultsABSTRACT
A novel plasmonic waveguide-coupled nanocavity with a monopole antenna is proposed to localize the optical power from a hybrid plasmonic waveguide and subsequently convert it into electrical current. The nanocavity is designed as a Fabry-Pérot waveguide resonator, while the monopole antenna is made of a metallic nanorod directly mounted onto the metallic part of the waveguide terminal which acts as the conducting ground. The nanocavity coincides with the antenna feed sandwiched in between the antenna and the ground. Maximum power from the waveguide can be coupled into, and absorbed in the nanocavity by means of the field resonance in the antenna as well as in the nanocavity. Simulation results show that 42% optical power from the waveguide can be absorbed in a germanium filled nanocavity with a nanoscale volume of 220 × 150 × 60 nm3. The design may find applications in nanoscale photo-detection, subwavelength light focusing and manipulating, as well as sensing.
ABSTRACT
A novel structure is proposed to electrically detect the plasmonic waves from a subwavelength plasmonic waveguide. By locating two L-shaped metallic nanorods in close proximity of each other at the end of the plasmonic waveguide, a metal-semiconductor-metal plasmonic detector is constructed. The L-shaped nanorods also form a dipole nanoantenna and a nanocavity to focus the photonic power into the active volume of the detector. The dimensions and locations of the L-shaped nanorods are studied to maximize the transmission efficiency of the photonic power from the plasmonic waveguide to the detector. Impedance matching with a sub is investigated to further improve the power transmission. Possible leads of the detector are discussed and their effects are investigated. Proposed detector has an ultra-compact and easy-to-fabricate planar structure, and a potentially THz speed, high responsivity as well as low power dissipation.
