超氧化物歧化酶的化学修饰

综述了超氧化物歧化酶活性部位和非活性部位的化学修饰,并对超氧化物歧化酶非活性部位修饰后的性质进行了讨论。     

单甲氧聚乙二醇化学修饰药物酶的研究进展

用单甲氧基聚乙二醉(1)化学修饰药物酶是生化药物研究开发的重要手段之一。本文综述了1化学修饰药物酶的一般方法及修饰后酶在生物和理化性质方面的变化，同时对1研究前景进行展望，并指出了尚待解决的问题。     

超氧化物歧化酶的化学修饰

<正> 蛋白质的化学修饰主要有两个目的:1.阐明蛋白质的结构,如酶的活性部位和氨基酸残基的存在状态;2.改变或增强蛋白质的的原有功能或赋予一些新的功能。超氧化物歧化酶(Superoxide dismutase,SGD)是广泛存在于生物体内的金属酶,     

蚯蚓纤溶酶的研究进展及趋势

综述了蚯蚓纤溶酶的理化性质、酶学性质、药效学特性、化学修饰及分子生物学等方面的研究进展 ,提出了蚯蚓纤溶酶研究领域的发展方向。     

化学修饰小干扰RNA作为治疗药物的研究进展

化学修饰为小干扰RNA（siRNA）治疗面临的诸多挑战提供了解决方法。此综述考察现有的各种siRNA修饰方法,包括RNA和双链siRNA结构的各个方面。然后考察化学修饰siRNA的应用,重点关注其作用的专一性（消除免疫反应和杂交依赖性的脱靶作用）和转运方法,同时对酶稳定性和效价也进行了讨论。     

锰超氧化物歧化酶模拟物的研究进展

超氧化物歧化酶(SOD)因能催化超氧离子(O*2)的歧化反应,而起到抗炎、抗衰老等作用.近年来,小分子化合物作为超氧化物歧化酶的模拟物越来越受到人们的重视.本文对锰超氧化物歧化酶(MnSOD)的活性部位及其模拟物的研究进展进行综述.     

蛋白质在生化制药上的应用

本文简述了利用蛋白质进行化学修饰的技术在生化制药领域的应用,同时提出在生产生化药品方面蛋白质化学修饰是一个重要的方法,并综述了对其未来发展的美好展望。     

蛋白质的化学修饰与生化药物

综述了为解除异体蛋白质的免疫原性、延长循环半衰期而进行的蛋白质化学修饰的进展，同时展望了蛋白质化学修饰的生化药物开发的进展，并强调蛋白质的化学修饰是生化药物研究开发的重要手段之一。     

影响铜锌超氧化物歧化酶活性的几个因素

影响铜锌超氧化物歧化酶活性的因素很多。溶液介电常数的增加减弱了酶分子活性中心附近ε－ＮＨ＾＋Ｏ＾２的静电吸引力，从而导致酶活的降低。Ｃｌ＾－浓度对ＣｕＺｎ－ＳＯＤ有明显的抑制作用是由于Ｃｌ＾－引起活性部位构象的变化。     

茯苓多糖的药理作用研究概况

茯苓多糖是从传统中药茯苓中提取的一种活性成分,其具有抗氧化、抗肿瘤、增强免疫力等多种药理作用,其应用前景广阔,随着我国对茯苓资源的进一步开发利用,对茯苓多糖药理作用的研究也越来越深入,同时对化学修饰后茯苓多糖的药理作用研究也越来越广泛,笔者通过查阅相关文献,对近年来茯苓多糖及其修饰物的药理作用研究作一综述,以期为进一步的研究作出参考。     

SOD特性改善技术研究进展

超氧化物歧化酶（SOD）的发现。为氧代谢的研究开创了新的局面。氧自由基被认为是机体重要的信号分子,参与了多种信号途径,与多种疾病的发生发展相关。SOD作为机体最重要的抗氧化酶体之一,直接清除机体产生的超氧自由基,阻止了机体的过氧化。但自然存在的SOD在体内代谢快。且分子量大,不易透过细胞膜而进入靶细胞,限制了其在机体内的应用。针对天然SOD的不足,早期国内外学者通过化学方法对其进行修饰研究,得到了多种修饰酶,为其在多领域的应用奠定了基础。近年来也有不少学者利用固定化酶技术、基因工程等手段对其进行特性改造。使其跨膜性、靶向性大大提升。成果显著。本文试图对国内外超氧化物歧化酶功能特性改善技术的研究进行概括。     

Effects of cadmium and dietary selenium on cytoplasmic and mitochondrial antioxidant defense systems in the heart of rats fed high dietary copper

Rats were fed a high copper diet (50 ppm copper) supplemented with 0, 0.1 and 0.5 ppm selenium and treated with either 50 ppm cadmium admixed with their feed or given 5 mg cadmium via osmotic minipumps. Only rats fed the low-selenium basal diet and treated with cadmium via the osmotic minipumps showed a significant rise in thiobarbiturate-reactive substances. This was associated with marked reductions in the activity of the selenoenzyme, glutathione peroxidase in heart cytosol and mitochondria. Cytosolic superoxide dismutase was unaffected and catalase activity was increased as a result of cadmium treatment. Dietary cadmium also resulted in marked reductions in the activities of cytosolic glutathione peroxidase, superoxide dismutase, and catalase. These biochemical lesions were not accompanied by decreases in the corresponding mitochondrial enzymes and no increase in thiobarbiturate-reactive substances was observed. Heart metal levels indicate the formation of cadmium-selenium complexes in rats treated with cadmium via the osmotic minipumps. Dietary cadmium does not appear to interact with selenium in a similar fashion. Heart copper levels were increased by dietary cadmium treatment. Thus, heart mitochondria appear to be the site of the primary biochemical lesion for cadmium and involve increased lipid peroxidation only when mitochondrial antioxidant defense enzymes are compromised.     

Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity

Cadmium treatment of rats maintained on a low-selenium diet produced a significant increase in specific heart weight together with histopathological changes. This increase was accompanied by a decrease in the activities of the selenoenzyme, glutathione peroxidase, and the copper-containing enzyme superoxide dismutase, together with a rise in thiobarbiturate-reactive substances in the heart. Increased dietary selenium prevented the lowering of glutathione peroxidase activity but did not influence the effect of cadmium on superoxide dismutase. The effect of cadmium on thiobarbiturate-reactive materials was markedly reduced in the rats fed high dietary selenium.     

Blood oxidative stress markers are unreliable markers of hepatic steatosis

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and viral hepatitis are associated with hepatic oxidative stress, which is partially dependent on the amount of hepatic fat. AIM: To determine whether the circulating lipid and oxidative stress parameters could be non-invasive markers of hepatic steatosis. METHODS: Sixty-four patients with NAFLD or viral hepatitis were tested for lipid peroxidation products and antioxidant defence systems, lipid parameters and liver function tests. RESULTS: Hepatic steatosis was correlated with lipids, gamma-glutamyltranspeptidase, thiobarbituric acid-reactive substances, superoxide dismutase and superoxide dismutase/erythrocyte glutathione peroxidase ratio. gamma-Glutamyltranspeptidase, triglycerides and low-density lipoprotein cholesterol were significantly higher in the presence of steatosis. No difference in blood oxidative stress markers was observed according to the presence or absence of steatosis except for the superoxide dismutase/erythrocyte glutathione peroxidase ratio. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were significantly higher in the NAFLD group (n = 17, 60% mean steatosis grade) than in the viral hepatitis group (n = 20, 13% mean steatosis grade). Only superoxide dismutase was lower and vitamin E higher in NAFLD than in viral hepatitis patients. CONCLUSIONS: Standard blood oxidative stress markers do not predict the extent of hepatic steatosis as they probably do not accurately reflect intrahepatic oxidative stress. Serum lipid levels were best correlated with hepatic steatosis.     

A superoxide-activated chemotactic factor and its role in the inflammatory process

Superoxide dismutase or derivatives thereof have been shown to be potent anti-inflammatory agents in several models of induced inflammation. In all cases, the anti-inflammatory effects included a marked suppression of the accumulation of inflammatory cells at the site of the potential lesion, suggesting a role for the superoxide radical in the chemotaxis process. The exposure of normal plasma to a source of superoxide in vitro resulted in the formation of a powerful chemotactic factor for human neutrophils. The factor is activated by reacting specifically with superoxide, and was found to consist of a complex of serum albumin and an unidentified lipid. The complex may be resolved and reconstituted. Both components are required for expression of biologic activity. The major mechanism for the anti-inflammatory activity of superoxide dismutase appears to be the prevention of the formation of this plasma-derived superoxide-dependent chemotactic factor.     

H2O2 production,modification of the glutathione status and methemoglobin formation in red blood cells exposed to diethyldithiocarbamate in vitro

Human red blood cells treated with the CuZn superoxide dismutase inhibitor diethyldithio-carbamate (DDC) undergo metabolic modifications in addition to the superoxide dismutase inhibition: oxidation of the reduced glutathione (GSH) to oxidized glutathione (GSSG), methemoglobin formation, and increased hexose monophosphate shunt activity were observed. The magnitudes of these changes are dependent on the DDC concentration. Under nitrogen, only superoxide dismutase inhibition occurs. After removal of the GSH with N-ethylmaleimide, production of H₂O₂ can be detected by measuring the red cell catalase inhibition in the presence of 3-amino-1,2,4-triazole. H₂O₂ production is not altered by conversion of oxyhemoglobin to methemoglobin by sodium nitrite prior to incubation. GSH oxidation and methemoglobin formation are stopped when DDC is eliminated from the incubation medium after completion of the superoxide dismutase inhibition. These data indicate that methemoglobin formation and modification of the GSH status in red cells treated by DDC are not a direct consequence of the CuZn Superoxide dismutase inhibition but are due rather to a DDC-dependent production of H₂O₂.     

Interaction of monensin and sulfadimethoxine in broilers, as mediated by hepatic microsomal cytochrome P-450 monooxygenases

The influence of monensin + sulfadimethoxine on cytochrome P-450 monooxygenase activity in broilers, and the possible consequences of modification of this system, including changes in blood levels of sulfadimethoxine, influence on the duration of xylazine-ketamine anesthesia, total antioxidant status and superoxide dismutase activity were studied. The results indicate that the combination of monensin + sulfadimethoxine gave a short-term inhibition of microsomal cytochrome P-450 monooxygenase activity but apparently did not influence the metabolism of other (exogenic) substances (ketamine, xylazine), and did not change the state of antioxidant systems or the relative liver weight. There was a rise in blood sulfadimethoxine levels.     

An automated analysis for superoxide dismutase enzyme activity

The pyrogallol autoxidation assay for superoxide dismutase was adapted for analysis by centrifugal analyzer. The precision of the enzymatic assay was estimated using bovine blood superoxide dismutase. Specific activity determined for human erythrocyte superoxide dismutase by the procedure agreed with previously reported determinations. Recovery of bovine blood superoxide dismutase from hemolysates provided a measure of proportional analytic error. Difficulties inherent in attempting to spectrophotometrically assay an enzyme catalyzing a reaction requiring a free radical substrate cannot be eliminated by an automated method. However, the centrifugal analyzer method makes routine enzymatic analysis for superoxide dismutase in numerous samples technically feasible. Moreover, automated analysis can conveniently include a standard such as bovine blood superoxide dismutase when enzyme levels in tissue extracts are assayed. These advantages make the method for assay of superoxide dismutase enzyme activity a useful procedure.     

Sympathetic denervation caused by long-term noradrenaline infusions; prevention by desipramine and superoxide dismutase.

1. The effects of continuous intravenous infusion of noradrenaline (0.01 and 0.1 microgram kg-1 h-1) were studied in both the infused lateral saphenous vein and the contralateral saphenous vein of normal dogs. Noradrenaline, saline, noradrenaline + desipramine or noradrenaline + superoxide dismutase were infused using Alzet osmotic minipumps. 2. After a 5 day infusion period, the noradrenaline content in plasma and in both saphenous veins was determined, and the venous tissues submitted to light microscope morphometry and ultrastructural study and used for the determination of their O-methylation capacity (with [3H]-isoprenaline as a substrate). 3. Noradrenaline caused dose-dependent damage to the sympathetic nerve endings of the lateral saphenous veins. Concomitant changes in extraneuronal structure and function were observed (hypertrophy of smooth muscle cells, nuclear dysmorphy, thickening of the vessel wall, impairment in O-methylation capacity). 4. Desipramine and superoxide dismutase prevented or reduced the effects of noradrenaline on both the morphological and the biochemical parameters; the protection afforded by superoxide dismutase was more marked than that by desipramine. 5. It is concluded that moderately high doses of noradrenaline exert a 6-hydroxydopamine-like effect and that this chemical sympathectomy is partially or totally prevented by desipramine or superoxide dismutase. The data suggest that a substance derived from noradrenaline, in the formation of which free oxygen radicals are involved and which is subject to neuronal uptake, is the chemical entity responsible for the neurotoxic effect observed.