Antioxidants Complement the Requirement for Protein Chaperone Function to Maintain ß-Cell Function and Glucose Homeostasis.

Proinsulin misfolding in the endoplasmic reticulum (ER) initiates a cell death response, although the mechanism(s) remains unknown. To provide insight into how protein misfolding may cause ß-cell failure, we analyzed mice with the deletion of P58(IPK)/DnajC3, an ER luminal co-chaperone. P58(IPK-/-) mice become diabetic as a result of decreased ß-cell function and mass accompanied by induction of oxidative stress and cell death. Treatment with a chemical chaperone, as well as deletion of Chop, improved ß-cell function and ameliorated the diabetic phenotype in P58(IPK-/-) mice, suggesting P58(IPK) deletion causes ß-cell death through ER stress. Significantly, a diet of chow supplemented with antioxidant dramatically and rapidly restored ß-cell function in P58(IPK-/-) mice and corrected abnormal localization of MafA, a critical transcription factor for ß-cell function. Antioxidant feeding also preserved ß-cell function in Akita mice that express mutant misfolded proinsulin. Therefore defective protein folding in the ß-cell causes oxidative stress as an essential proximal signal required for apoptosis in response to ER stress. Remarkably, these findings demonstrate that antioxidant feeding restores cell function upon deletion of an ER molecular chaperone. Therefore antioxidant or chemical chaperone treatment may be a promising therapeutic approach for type 2 diabetes.

Dye-sensitized solar cells using polymer electrolytes based on poly(vinylidene fluoride-hexafluoro propylene) nanofibers by electrospinning method.

The dye-sensitized solar cell (DSSC) devices using polymer electrolytes based on electrospun poly(vinylidene fluoride-hexafluoro propylene) (PVDF-HFP) nanofibers were fabricated and investigated the photovoltaic performances. The electrospun PVDF-HFP nanofibers were prepared by various parameters such as; polymer concentrations, applied voltages, and tip to collector distances (TCD) by the electrospinning method. The open circuit voltage (V(OC)), short circuit current (J(SC)), fill factor (FF), and overall power conversion efficiency (eta) of DSSC devices using electro-spun PVDF-HFP nanofibers were 0.7180-0.7420 V, 9.7200-10.8837 mA/cm2, 0.5610-0.6250, and 4.1700-5.0186%, respectively. When 15 wt% of polymer concentration, 14 kV of applied voltage, and 14 cm of TCD is applied to fabricate the PVDF-HFP nanofiber, the electrospun PVDF-HFP nanofiber should be the regular diameter of a nanofiber, the power conversion efficiency of the DSSC device reached 5.0186% as the best result.

Structure and function of RGD peptides derived from disintegrin proteins.

The Arg-Gly-Asp (RGD) sequence serves as the primary recognition site in extracellular matrix proteins, and peptides containing this sequence can mimic the biological activities of matrix proteins. We have initiated structure-function studies of two RGD containing peptides, RGD-5(AGGDD) and cyclic RGD-6(CARGDDC). Assays have shown that cyclic RGD-peptides inhibit platelet aggregation more efficiently than linear ones. NMR data revealed that RGD-5 and RGD-6 have entirely different conformation. RGD-5 has a linear extended structure and RGD-6 has a stable loop conformation. In RGD-5 the guanidinium group of Arg2 and the carboxyl group of Asp4 lie in parallel, whereas the side-chains of Arg3 and Asp5 of RGD-6 are located in different planes, supporting the idea that the stability of the cyclic form derives from the packing of the side chain of the Arg and Asp residues. The structural features of these peptides could provide a basis for designing new drugs against diseases related to platelet aggregation and as cancer antagonists.