|
| ||
|
|
||
Central Molecule (central + molecule)
Selected AbstractsStructure and biology of complement protein C3, a connecting link between innate and acquired immunityIMMUNOLOGICAL REVIEWS, Issue 1 2001Arvind Sahu Summary: Complement protein C3 is a central molecule in the complement system whose activation is essential for all the important functions performed by this system. After four decades of research it is now well established that C3 functions like a double-edged sword: on the one hand it promotes phagocytosis, supports local inflammatory responses against pathogens, and instructs the adaptive immune response to select the appropriate antigens for a humoral response; on the other hand its unregulated activation leads to host cell damage. In addition, its interactions with the proteins of foreign pathogens may provide a mechanism by which these microorganisms evade complement attack. Therefore, a clear knowledge of the molecule and its interactions at the molecular level not only may allow the rational design of molecular adjuvants but may also lead to the development of complement inhibitors and new therapeutic agents against infectious diseases. A.S. is a Wellcome Trust Overseas Senior Research Fellow in Biomedical Science in India. This research was supported by National Institutes of Health grants AI 30040, GM 56698, HL28220, and AI 48487. [source] Refractive index and third-order nonlinear susceptibility of C60 in the condensed phase calculated with the discrete solvent reaction field modelINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 5 2005L. Jensen Abstract We have calculated the frequency-dependent refractive index and the third-order nonlinear susceptibility for C60 in the condensed phase, which is related to third-harmonic generation (THG) and degenerate four-wave mixing (DFWM) experiments. This was done using the recently developed discrete solvent reaction field (DRF) model, which combines a time-dependent density functional theory (TD-DFT) description of the central C60 molecule with a classical polarizable MM model for the rest of the fullerene cluster. Using this model, effective microscopic properties can be calculated that, combined with calculated local field factors, give macroscopic susceptibilities. The largest calculation was for a cluster of 63 C60 molecules in which the central molecule was treated with TD-DFT. For this molecule, the effective polarizability was increased with about 15% and the effective second hyperpolarizability with about 60% compared with the gas phase. The calculated refractive index was found to be in good agreement with experiments and other theoretical results. The agreement with THG experiments was within a factor of two, whereas for DFWM the agreement was less good due to the neglect of vibrational contributions in the calculations. It was found that it is more important to account for the dispersion in the third-order susceptibilities than in the corresponding second hyperpolarizability. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] Interactions between melatonin and nicotinamide nucleotide: NADH preservation in cells and in cell-free systems by melatoninJOURNAL OF PINEAL RESEARCH, Issue 2 2005Dun-Xian Tan Abstract:, Interactions of melatonin and nicotinamide adenine dinucleotide (NADH) have been studied in different experimental models including NADH-promoted oxyhemoglobin oxidation, vanadate-induced NADH oxidation and paraquat-induced NADH depletion in cultured PC12 cells. Our findings indicate that melatonin preserves NADH levels under oxidative stress both in cell-free systems and in cultured PC12 cells. These interactions likely involve electron donation by melatonin and reduction of the NAD radical. As a result, the NAD radical is recycled to NADH and melatonin is oxidized to N1 -acetyl- N2 -formyl-5-methoxykynuramine (AFMK). NADH is a central molecule at the crossroads between energy metabolism and the antioxidant defense system in organisms. Recycling of NADH by melatonin might improve the efficiency of NADH as an energy carrier and as an antioxidant. Interactions between melatonin and NADH may be implicated in mitochondrial metabolism. [source] 2133: p62/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in human retinal pigment epithelial cellsACTA OPHTHALMOLOGICA, Issue 2010K KAARNIRANTA Purpose The pathogenesis of age-related macular degeneration involves impaired protein degradation in retinal pigment epithelial (RPE) cells. The ubiquitin-proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Prior to proteolysis, heat shock proteins (HSPs) attempt to refold stress ,induced misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. The functional roles of p62 and HSP70 were evaluated in conjunction with protesome inhibitor -induced autophagy in human RPE cells (ARPE-19). Methods The p62, HSP70 and ubiquitin protein levels and localization were analyzed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. The p62 and HSP70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. Results Proteasome inhibition evoked the accumulation of p62 and HSP70 that strongly co-localized with each other in perinuclear aggregates. The p62 accumulation was time and concentration dependent after MG-132 proteasome inhibitor loading. Interestingly, autophagy induction was p62 and Hsp70 independent. In addition, the p62 silencing decreased the ubiquitination level of the perinuclear aggregates. Recently we showed that hsp70 mRNA depletion increased cell death in ARPE-19 cells. Here we now demonstrate that p62 mRNA silencing has similar effects on cellular viability. Conclusion The p62 and HSP70 are central molecules in the regulation of protein turnover in human retinal pigment epithelial cells in proteasome inhibitor- induced autophagy. [source] | ||||||||||