Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis

Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular- superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC- SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1β, TNFα, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.     

Superoxide Dismutase Biosensors for Superoxide Radical Analysis

ABSTRACT

Some basic work has been performed on the development and optimisation of superoxide dismutase (SOD) biosensors for superoxide radical analysis. Initially we studied the possibility of obtaining a SOD biosensor using the Clark electrode as indicating sensor. However, the best results were obtained using as indicator a classical amperometric electrode for H₂O₂. In both cases the superoxide radical was generated in situ using the xanthine/xanthine oxidase (XOD) enzyme system, while the SOD was immobilised in kappa-carrageenan gel. The first application was realised by studying the effects in vitro on the superoxide radical of some molecules commonly accepted as radical scavengers.     

Principles of Sensorial Radical Detection-A Minireview

ABSTRACT

For the short-lived species nitric oxide and superoxide various sensor approaches for their detection have been reviewed. Sensors provide access to a time and spatially resolved analysis basing a deeper insight into the physiological role and interaction of both radicals. Superoxide sensing is mainly based on electrodes modified with cytochrome c or superoxide dismutase as recognition elements. For NO quantification optrodes as well as electrodes can be used, with a higher sensitivity for the latter. Electrodes were modified with transition metal complexes, simple gas permeable membranes or heme proteins.     

铅染毒家兔脂质过氧化水平和神经传导速度的变化及关系研究

为观察铅对脂质过氧化水平和神经传导速度(NCV)的影响,并探讨两者关系,1 6只家兔随机分为2组,每组8只,染铅组饮用0 1 %醋酸铅水,对照组予以去离子水,持续8周,测定了两组家兔股神经NCV及血浆和脑组织丙二醛(MDA)、总超氧化物歧化酶(T -SOD)水平,分析了MDA、T -SOD与NCV之间的关系。结果表明,染铅组NCV显著低于对照组(P <0 0 1 ) ,NCV与脑组织MDA之间存在相关关系(r=-0 5 2 1 ,P <0 0 5 ) ,但染铅组MDA、T -SOD与对照组比较未达到显著性差别(P >0 0 5 )。提示铅中毒能引起NCV减慢,这与脂质过氧化水平有关,脂质过氧化损伤可能是铅致中毒性周围神经病的机制之一。     

Oligomerization,Isomerization and Carboxylation of Alkanes and Alkenes with Galvanostatically Generated Superoxide in the Al/O2 Electrochemical Cell

Conversion of low‐value, but thermodynamically stable chemical byproducts such as alkanes or CO₂ to more valuable feedstocks is of broad‐based interest. These so‐called up‐conversion processes are expensive because they require energy‐intensive and catalytic interventions to drive reactions against thermodynamic gradients. Here we show that the nucleophilic characteristics of superoxides, generated galvanostatically in an Aluminum/O₂ electrochemical cell, can be used in tandem with the intrinsic catalytic properties of an imidazolium/AlCl₃ electrolyte to facilely upgrade alkanes (n‐decane), alkenes (1‐decene), and CO₂ feedstocks. The aluminum/O₂ electrochemical cell used to generate the superoxide intermediate is also reported to deliver large amounts of electrical energy and therefore offers a system for high‐energy density storage and for chemical up‐conversion of low‐value compounds. Chronopotentiometry, mass spectrometry and nuclear magnetic resonance were used to investigate the electrochemical features of the system and to analyze the discharge products. We find that even at room temperature, alkanes and alkenes are facilely oligomerized and isomerized at high conversions (>97 %), mimicking the traditionally produced refined products. Incorporating CO₂ in the alkane feed leads to formation of esters and formates at moderate yields (21 %).     

Effect of Cation Size on Solvation and Association with Superoxide Anion in Aprotic Solvents

Influence of cation size on solvation strength, diffusion, and kinetics of the association reaction with anions O₂⁻ in aprotic solvents, such as acetonitrile and dimethyl sulfoxide, has been investigated by means of molecular dynamics simulations. The work is motivated by the need to understand the molecular nature of the solvent-induced changes in capacity of Li-air batteries. We have shown that the dependence of the solvation shell stability on the cation size has a maximum at a particular ion radius that corresponds to a solvent coordination number of 4. The shell stability maximum coincides with the diffusion coefficient minimum. The variation of the cation shell stability has a crucial impact on the kinetics of the cation-O₂⁻ association. We have demonstrated that profound inhibition of the association reaction for Li⁺ in dimethyl sulfoxide is a result of the lock-and-key effect that cannot be described in the framework of Hard Soft Acid Base theory.     

Electronic and Functional Structure of Copper in Plant Cu/Zn Superoxide Dismutase with Combined Site-directed Mutagenesis and Electron Paramagnetic Resonance

Arabidopsis thaliana copper-zinc superoxide dismutase 1 (AtSOD1) is a typical metalloenzyme conferring cellular protection against the excessive accumulation of toxic reactive oxygen species, and is therefore considered as a critical protein. However, the structure and function of the vital amino acids around the active site of AtSOD1 remain poorly understood. Herein, the coordinated geometry of the catalytic center in AtSOD1 was reconstructed by electron paramagnetic resonance (EPR) technique, and it was found to be composed of copper and four histidine (H) residues using site-directed mutagenesis. Analysis of the mutants showed that H45 and H62 play essential roles in the catalytic reaction, and H119 plays an accessary role in facilitating substrate or proton transfer. The results indicated that the redox change of the Cu ion and the overall enzymatic activity of the protein were sustained by the H45-Cu-H62 core structure. In contrast, the residue H47 showed nearly no effect on the SOD catalytic activity. These data should contribute to a deeper understanding of the catalytic mechanism of the enzyme, and provide a new approach for the effective molecular modification of copper/zinc SODs to facilitate further research in this field.     

Reactivity of C4‐indolyl substituted 1,4‐dihydropyridines toward superoxide anion (O2•) in dimethylsulfoxide

Reactivity of two new C4‐indolyl substituted 1,4‐dihydropyridines (1,4‐DHPs) toward superoxide anion (O₂^? ) in dimethylsulfoxide (DMSO) is reported. Reactivity was followed by electrochemical and spectroscopic techniques. Gas chromatography‐mass spectrometry (GC–MS) was used to identify the final products of the reaction. C4 indolyl‐substituted‐1,4‐DHPs reacted toward O₂^? at significant rates, according to the calculated kinetic rate constants. Results are compared with 4‐phenyl‐DHP and the commercial 1,4‐DHPs, nimodipine, nisoldipine, and amlodipine. Indolyl‐substituted 1,4‐DHPs were more reactive than the commercial derivatives. The direct participation of proton of the 1‐position of the secondary amine in the quenching of O₂^? was demonstrated. Copyright © 2008 John Wiley & Sons, Ltd.     

铜锌超氧化物歧化酶的突变与神经退行性紊乱的生物无机化学

本文简单介绍了铜锌超氧化物歧化酶的结构、功能及其相互关系,较为详细地讨论了与神经退行性紊乱,尤其是与肌萎性脊髓侧索硬化症有关的铜锌超氧化物歧化酶突变体的生物无机化学的研究进展,提出由该酶突变而引起的蛋白质局部结构变化和金属离子缺失,以及由此导致的氧化损伤和聚集作用可能是导致神经退行性紊乱的主要原因之一.