Titanium dioxide with a mesoporous structure, when photoactivated in water, demonstrates an unprecedented photocatalytic activity, driven strongly by an adsorption degree of molecules onto the catalyst surface, which promotes a preferential conversion of a well-adsorbed molecule. This catalyzes a selective transformation of a well-adsorbed molecule into a less-adsorbed molecule, so-labeled "stick-and-leave" transformation, which promotes a direct hydroxylation of benzene to phenol, one of the most difficult synthetic reactions, with very high selectivity (>80%) and using water as a source of oxidant.

CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time-and dose-dependent manner for

No abstract

Pancreatic beta-cells are susceptible to reactive oxygen species (ROS), which are known to be generated by high or low glucose (LG), hypoxic, or cytokine-producing conditions. When we cultured mouse beta-cell-derived MIN6 cells in a LG condition, we detected a significant generation of ROS, including hydrogen peroxide, which was comparable to the ROS production in hypoxic or cytokine-treated conditions. ROS accumulation induced by the LG culture led to cell death, which was prevented by the ROS scavengers N-acetylcysteine and manganese(III)tetrakis(4-benzoic acid) porphyrin. We next investigated the mechanism of stress-activated protein kinases (SAPKs), c-jun N-terminal kinase (JNK) and p38, in ROS-induced MIN6 cell death. Activation of p38 occurred immediately after the LG culture, whereas JNK activation increased slowly 8 h later. Adenoviral p38 expression decreased MIN6 cell death, whereas the JNK expression increased it. Consistently, blocking p38 activation by inhibitors increased beta-cell death, whereas JNK inhibitors decreased it. We then examined the role of MAPK phosphatases (MKPs) specific for stress-activated protein kinases in beta-cell death. We found that MKP-1 presented an increase in its oxidized product after the LG culture. ROS scavengers prevented the appearance of this oxidized product and JNK activation. Thus, ROS-induced MKP inactivation causes sustained activation of JNK, which contributes to beta-cell death. Adenoviral overexpression of MKP-1 and MKP-7 prevented the phosphorylation of JNK at 36 h after the LG culture, and decreased MIN6 beta-cell death. We suggest that beta-cell death is regulated by interactions between JNK and its specific MKPs.

No abstract

1OBJECTIVE-Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic ␤-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in ␤-cells by an RNA interference technique. RESEARCH DESIGN AND METHODS-Adenovirus-mediated expression of short hairpin RNA specific for phogrin (shPhogrin) was conducted using cultured ␤-cell lines and mouse islets. Both glucose-stimulated insulin secretion and cell proliferation rate were determined in the phogrin-knockdown cells. Furthermore, protein expression was profiled in these cells. To see the binding partner of phogrin in ␤-cells, coimmunoprecipitation analysis was carried out. RESULTS-Adenoviral expression of shPhogrin efficiently decreased its endogenous expression in pancreatic ␤-cells. Silencing of phogrin in ␤-cells abrogated the glucose-mediated mitogenic effect, which was accompanied by a reduction in the level of insulin receptor substrate 2 (IRS2) protein, without any changes in insulin secretion. Phogrin formed a complex with insulin receptor at the plasma membrane, and their interaction was promoted by high-glucose stimulation that in turn led to stabilization of IRS2 protein. Corroboratively, phogrin knockdown had no additional effect on the proliferation of ␤-cell line derived from the insulin receptor-knockout mouse. CONCLUSIONS-Phogrin is involved in ␤-cell growth via regulating stability of IRS2 protein by the molecular interaction with insulin receptor. We propose that phogrin and IA-2 function as an essential regulator of autocrine insulin action in pancreatic ␤-cells. Diabetes 58:682-692, 2009 G lucose is a principle regulator of pancreatic ␤-cell survival and growth as well as insulin secretion (1). It is a potent mitogen on pancreatic ␤-cells and regulates islet ␤-cell mass through their replication (2). Recent studies have suggested that insulin secreted in response to elevated glucose exerts autocrine/paracrine effects, including promotion of insulin biosynthesis and proliferation of ␤-cells (3,4). The importance of insulin signaling in maintaining ␤-cell mass was demonstrated by targeted knockouts of the insulin receptor and insulin receptor substrate 2 (IRS2) (5-8). Although insulin receptor knockout had a restricted effect on ␤-cell mass (7), its mitogenic function on ␤-cells was clearly shown by short interfering RNA (siRNA)-based silencing of insulin receptor in ␤-cell-derived MIN6 cells (9,10). More recently, another pathway was demonstrated showing that glucose metabolism leads to increased ␤-cell mass through the transcriptional activation of IRS2 (11). Calcium/calmodulin-dependent protein kinases and increased cAMP levels were suggested to contribute to IRS2 expression, and this pathway has been shown to be modulated by the incretin hormone glucagonlike peptide 1 (GLP-1) (12,13). In both cases, IRS2 must be a key mediator for glucose-responsive ␤-cell growth (14).Phogrin (IA-2␤) and IA-2 (ICA51...

Titanosilicate molecular sieves, when activated by ultraviolet light irradiation in water in the presence of molecular oxygen, catalyze a conversion of molecules having a size close to the pore of the catalysts but are inactive for molecules having much larger or smaller size. This unprecedented size-screening photocatalytic activity is triggered by a combination of H2O-induced shortened lifetime of active species (charge-transfer excited state of tetrahedrally coordinated titanium oxide) and restricted diffusion of a molecule inside the pore. This catalytic property demonstrates a potential utility of the catalyst for selective transformation of molecules that is associated with a size reduction of molecules, so-labeled "molecular shave" transformation.

Phogrin is an integral glycoprotein primarily expressed in neuroendocrine cells. The predominant localization of phogrin is on dense-core secretory granules, and the lumenal domain has been shown to be involved in its efficient sorting to the regulated secretory pathway. Here, we present data showing that a leucine-based sorting signal [EExxxIL] within the cytoplasmic tail contributes its steady-state localization to secretory granules. Deletion mutants in the tail region failed to represent granular distribution in pancreatic b-cell line, MIN6, and anterior pituitary cell line, AtT-20. A sorting signal mutant with two glutamic acids substituted into alanines (EE/AA) is primarily accumulated in the Golgi area instead of secretory granules, and another mutant (IL/AA) is trapped at the plasma membrane due to a defect in endocytosis. We further demonstrate that the leucine-based sorting signal of phogrin specifically interacts with both adaptor protein AP-1 and AP-2 clathrin adaptor complexes in vitro. These observations, along with previous studies, suggest that distinct domains of phogrin mediate proper localization of this transmembrane protein on secretory granules.