Enhanced endoplasmic reticulum (ER) stress has been implicated in various pathological situations including inflammation. During a search for compounds that regulate ER stress, we identified vaticanol B, a tetramer of resveratrol, as an agent that protects against ER stress-induced cell death. Vaticanol B suppressed the induction of unfolded protein response-targeted genes such as glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) after cells were treated with ER stressors. Analysis in the mouse macrophage cell line RAW 264.7 revealed that vaticanol B also possesses a strong anti-inflammatory activity. Production of a variety of inflammatory modulators such as tumor necrosis factor-alpha, nitric oxide, and prostaglandin E(2) was inhibited by vaticanol B to a much greater extent than by monomeric or dimeric resveratrol after exposure of cells to lipopolysaccharide. Further investigations to determine the common mechanisms underlying the regulation of ER stress and inflammation by vaticanol B disclosed an important role for vaticanol B in regulation of basic gene expression and in prevention of the protein leakage from the ER into the cytosol in both conditions. These results suggest that vaticanol B is a novel anti-inflammatory agent that improves the ER environment by reducing the protein load on the ER and by maintaining the membrane integrity of the ER.

O. A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress.

Although intracellular stresses are believed to be involved in the process of neurodegeneration, it is not fully understood how one stress ⁄ stress response affects another. Herp is an endoplasmic reticulum (ER)-located membrane protein proposed to function in ER-associated degradation (ERAD). Herp is strongly induced by ER stress but rapidly degraded by proteasome. To elucidate the effect of Herp expression on proteolytic stress caused by impairment of the ubiquitin-proteasome system (UPS), we utilized 293T Herp knockdown (KD) cells and F9 Herp knockout cells. Knockdown of Herp gene unexpectedly facilitated the degradation of Parkinson's disease-associated cytosolic proteins such as a-synuclein and its binding partner, synphilin-1, and improved cell viability during proteasomal inhibition. A similar tendency was observed in F9 Herp knockout cells transfected with synphilin-1. Herp temporarily bound to a-synuclein, synphilin-1 and the E3 ligase SIAH1a during proteolytic stress but not during ER stress. Furthermore, deletion of Herp enhanced the amount of ubiquitinated protein in the cytosol during proteasomal inhibition, although it did not affect the activity or expression of proteasome. These results suggest that ERAD molecule Herp may delay the degradation of cytosolic proteins at the ubiquitination step.

Monodispersed spherical particles are potentially available for various applications as building blocks for photonic crystals, chromatography stationary phase, and drug support for controlled release. Immobilization of a molecular recognizable unit to the surface of the spherical particles is important in such applications. Here we report that silica spheres of submicrometer size were covered by a swellable layered silicate, which plays a role in accommodating cationic species. The coverage was conduced by using colloidal monodispersed silica spheres as a sacrificial template in the presence of urea and layered silicate sources (LiF and MgCl2) at 373 K. X-ray diffraction peaks ascribed to hectorite (smectite group of layered clay) were observed in the resulting solid. The zeta potential distribution of the resulting solid had a single peak and shifted from that of the original silica. Transmission electron microscopy (TEM) observations revealed that stacks of the silicate layers lay on the surface of the silica core. Quantitative ion exchange reactions of the interlayer cations with a cationic surfactant were shown. The layered silicate was firmly glued onto the silica particles because the silicate with a cationic dye did not flake off from the product.