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1.
Children with growth dysfunction present complex diagnostic challenges. The purpose of this study was to determine the effects of oral zinc treatment on red cell copper/zinc superoxide dismutase (Cu/Zn-SOD) activity and copper and zinc concentrations in children with “growth retardation.” Twenty-nine patients, average age of 11 yr, whose percentile was under 3% of the National Center of Health Statistics parameters were selected. For the control group, 10 children whose average age was 10 yr were included. Red cell Cu/Zn-SOD activity was determined by spectrophotometer. Red cell copper and zinc concentrations were measured by atomic absorption spectrophotometer. Red cell Cu/Zn-SOD activity was higher than the control group before zinc treatment (p<0.001). There was a decrease in the Cu/Zn-SOD activity after zinc treatment, but the mean value of the Cu/Zn-SOD activity of patients was still higher than the control values (p<0.001). After zinc treatment, there was an increase in red cell zinc concentration (p<0.01) and a decrease in copper concentration (p<0.001), which were statistically significant. The results of this study suggested that Cu/Zn-SOD activity was increased significantly during growth retardation and zinc treatment appeared to ameliorate the enzyme activity. There were also insignificant alterations in red cell copper and zinc concentrations. Presented at the 23rd Congress of Endocrinology and Metabolic Diseases of Turkey Joint Meeting with the European Federation of Endocrine Societies, Bilkent Hotel, Ankara, 7–9 September, 2000.  相似文献   

2.
We hypothesized that plasma extracellular superoxide dismutase (EC-SOD) activity reflects the zinc nutriture of healthy pregnant women. Sixty-three women were selected from 580 African-American women who participated in a clinical trial to evaluate the effect of prenatal zinc supplementation on pregnancy outcome. Half of the women received zinc (25 mg/d) and the other half was given a placebo from about 19 wk gestation to delivery. In the trial, a positive effect of zinc supplementation on birthweight was observed, indicating that the population as a whole had suboptimal zinc nutriture. Using plasma samples obtained during the trial, EC-SOD activities were measured and the values were compared with plasma zinc concentrations and plasma alkaline phosphatase activities. Plasma EC-SOD activities in our subjects were lower than previously published values for healthy adults in Korea. Although plasma EC-SOD activity may reflect severe zinc deficiency, it is not a sensitive marker for marginal deficiency status. Plasma EC-SOD activities did not prove to be a better indicator of zinc nutriture of pregnant women than either plasma zinc or plasma alkaline phosphatase activities.  相似文献   

3.
All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS). These mutations, mostly of a familial nature (ALS 1, MIM 105400), span all of the coding region of this enzyme except for a highly conserved centrally located domain that includes all of exon III. We describe the identification and characterization of two mutations in this region, both found in mice. One mutation, a glutamate to lysine amino acid substitution was found in position 77 (E77K) of the strain SOD1/Ei distributed by the Jackson Laboratory. The other mutation, a lysine to glutamate substitution at position 70 (K70E) of a human transgene, was discovered in mouse line TgHS/SF-155. Enzyme activity measurements and heterodimer analysis of the CuZn SOD variant in SOD1/Ei suggest a mild loss of activity, which differs from the enzyme activity losses detected in patients with autosomal dominant ALS 1. Similarly, the presence of the mutant transgene in TgHS/SF 155 does not produce any phenotypic manifestations.  相似文献   

4.
The CuZn superoxide dismutase (SOD1), a member of a group of isoenzymes involved in the scavenger of superoxide anions, is a dimeric carbohydrate free protein, mainly localized in the cytosol. The reactive oxygen species (ROS) are involved in many pathophysiological events correlated with mutagenesis, cancer, degenerative processes and aging. In the first part of this mini-review the well known role of SOD1 and ROS are briefly summarized. Following, a potential novel biological action that SOD1 could exert is described, based on the recent researches demonstrating the secretion of this enzyme in many cellular lines. Moreover, the role of impaired mutant SOD1 secretion, associated with cytoplasmic toxic inclusion, which occurs in familial amyotrophic lateral sclerosis (ALS), is summarized. In addition, a depolarization-dependent release of SOD1 in pituitary GH3 cells and in rat synaptosomes through a calcium and SNARE-dependent mechanism is reported.  相似文献   

5.
The aim of the study was to evaluate the antioxidative Cu/Zn-SOD (superoxide dismutase) response to obesity-related stress in obese children compared to a similar-aged control group. Forty-eight exogenic obese children and 11 healthy children were compared for red cell Cu/Zn-SOD, glucose, and lipid profiles and the relations between the were investigated. Antioxidant response as Cu/Zn-SOD was significantly higher in the obese group (p<0.05). Although glucose and lipid levels were statistically higher in the obese group, a certain relation with the SOD level was not established in childhood. This is the first study showing the oxidative stress caused by obesity and related antioxidative response even in the childhood period. Interventions, including diet modifications, should be kept in mind to diminish the obesity-related oxidative stress from the childhood period.  相似文献   

6.
Extracellular superoxide dismutase   总被引:1,自引:0,他引:1  
The extracellular space is protected from oxidant stress by the antioxidant enzyme extracellular superoxide dismutase (EC-SOD), which is highly expressed in selected tissues including blood vessels, heart, lungs, kidney and placenta. EC-SOD contains a unique heparin-binding domain at its carboxy-terminus that establishes localization to the extracellular matrix where the enzyme scavenges superoxide anion. The EC-SOD heparin-binding domain can be removed by proteolytic cleavage, releasing active enzyme into the extracellular fluid. In addition to protecting against extracellular oxidative damage, EC-SOD, by scavenging superoxide, preserves nitric oxide bioactivity and facilitates hypoxia-induced gene expression. Loss of EC-SOD activity contributes to the pathogenesis of a number of diseases involving tissues with high levels of constitutive extracellular superoxide dismutase expression. A thorough understanding of the biological role of EC-SOD will be invaluable for developing novel therapies to prevent stress by extracellular oxidants.  相似文献   

7.
Two cyanide-sensitive and organic solvent-inactivated superoxide dismutase isoenzymes were purified from pea leaves, Pisum sativum, cv Thomas Laxto  相似文献   

8.
To identify biomarkers associated with the development of hepatocellular carcinoma (HCC) in CuZn superoxide dismutase (CuZnSOD, Sod1) deficient mice, 2-DE followed by MS analysis was carried out with liver samples obtained from 18-month-old Sod1-/- and +/+ mice. The intracellular Ca binding protein, regucalcin (RGN), showed a divergent alteration in Sod1-/- samples. Whereas elevated RGN levels were observed in -/- samples with no obvious neoplastic changes, marked reduction in RGN was observed in -/- samples with fully developed HCC. GST mu1 (GSTM1), on the other hand, showed a significant increase only in the neoplastic regions obtained from Sod1-/- livers. No change in GSTM1 was observed in the surrounding normal tissues. Marked reduction was observed in two intracellular lipid transporters, fatty acid binding protein 1 (FABP1) and major urinary protein 11 and 8 (MUP 11&8), in Sod1-/- samples. Analysis of additional samples at 18-22 months of age showed a three-fold increase in enolase activities in Sod1-/- livers. Consistent with previous findings, carbonic anhydrase 3 (CAIII) levels were significantly reduced in Sod1-/- samples, and immunohistochemical analysis revealed that the reduction was not homogenous throughout the lobular structure in the liver.  相似文献   

9.
超氧化物歧化酶在临床上的应用   总被引:1,自引:0,他引:1  
对超氧化物歧化酶(SOD)、重组人SOD(rh-SOD)在临床上的应用进行了概括和介绍。动物来源的SOD目前主要应用于治疗肿瘤放疗的后遗症、各种炎症以及多种皮肤病,rh-SOD则较多应用于心脏、肾脏等器官的保护和移植过程以及心血管疾病的治疗。  相似文献   

10.
11.
12.
Superoxide dismutases (SODs) are a family of metalloenzymes that catalyze the dismutation of superoxide anion radicals into molecular oxygen and hydrogen peroxide. Iron superoxide dismutases (FeSODs) are only expressed in some prokaryotes and plants. A new and highly active FeSOD with an unusual subcellular localization has recently been isolated from the plant Vigna unguiculata (cowpea). This protein functions as a homodimer and, in contrast to the other members of the SOD family, is localized to the cytosol. The crystal structure of the recombinant enzyme has been solved and the model refined to 1.97 A resolution. The superoxide anion binding site is located in a cleft close to the dimer interface. The coordination geometry of the Fe site is a distorted trigonal bipyramidal arrangement, whose axial ligands are His43 and a solvent molecule, and whose in-plane ligands are His95, Asp195, and His199. A comparison of the structural features of cowpea FeSOD with those of homologous SODs reveals subtle differences in regard to the metal-protein interactions, and confirms the existence of two regions that may control the traffic of substrate and product: one located near the Fe binding site, and another in the dimer interface. The evolutionary conservation of reciprocal interactions of both monomers in neighboring active sites suggests possible subunit cooperation during catalysis.  相似文献   

13.
14.
Two immunoassays have been developed for the determination of rat erythrocyte dismutase (Cu,Zn-SOD). An enzyme-linked immunosorbent assay (ELISA) was very sensitive down to 4 ng/ml with a coefficient of variation (CV) of 18% while the single radial immunodiffusion assay (SRID) permitted an adequate detection level (5 μg/ml) with far better accuracy (CV = 4.2%). The latter was thus selected for the determination of Cu,Zn-SOD in the red blood cells of normal and copper-depleted rats. The average value of Cu,Zn-SOD in normal adult rat erythrocytes was 1142 ± 120 ng/mg hemoglobin. When compared to activity measurements, good correlation was obtained between enzyme content and enzyme activity (r = 0.803, P < .001). In an experimental copper deficiency followed by supplementation, good correlation was observed in the course of depletion (r = 0.848, P < .001) and repletion (r = 0.896, P < .001). During depletion, the loss of enzyme activity was mainly related to a loss of enzyme. However, enzymatically inactive protein was formed which would be activated when copper was added. These results indicate the importance of a combined use of Cu,Zn-SOD immunoquantitation and activity measurements to enable a better understanding of changes occuring with respect to enzyme activity.  相似文献   

15.
The known action of Cu, Zn superoxide dismutase (holo SOD) that converts O2 to O2 and H2O2 plays a crucial role in protecting cells from toxicity of oxidative stress. However, the overproduction of holo SOD does not result in increased protection but rather creates a variety of unfavorable effects, suggesting that too much holo SOD may be injurious to the cells. In the in vitro study, we report a finding that the holo SOD from bovine erythrocytes and its apo form possess a divalent-metal-dependent nucleolytic activity, which was confirmed by UV–vis absorption titration of calf thymus DNA (ctDNA) with the holo SOD, quenching of holo SOD intrinsic fluorescence by ctDNA, and by gel electrophoresis monitoring conversion of DNA from the supercoiled DNA to nicked and linear forms, and fragmentation of a linear λDNA. Moreover, the DNA cleavage activity was examined in detail under certain reaction conditions. The steady-state study indicates that DNA cleavage supported by both forms of SOD obeys Michaelis–Menten kinetics. On the other hand, the assays with some other proteins indicate that this new function is specific to some proteins including the holo SOD. Therefore, this study reveals that the divalent-metal-dependent DNA cleavage activity is an intrinsic property of the holo SOD, which is independent of its natural metal (copper and zinc) sites, and may provide an alternative insight into the link between SOD enzymes and neurodegenerative disorders.  相似文献   

16.
In the present study the light induced formation of superoxide and intrinsic superoxide dismutase (SOD) activity in PS II membrane fragments and D1/D2/Cytb559-complexes from spinach have been analyzed by the use of ferricytochrome c (cyt c(III)) reduction and xanthine/xanthine oxidase as assay systems. The following results were obtained: 1.) Photoreduction of Cyt c (III) by PS II membrane fragments is induced by addition of sodium azide, tetracyane ethylene (TCNE) or carbonylcyanide-p-trifluoromethoxy-phenylhydrazone (FCCP) and after removal of the extrinsic polypeptides by a 1M CaCl2-treatment. This activity which is absent in control samples becomes completely inhibited by the addition of exogenous SOD. 2.) The TCNE induced cyt c(III) photoreduction by PS II membrane fragments was found to be characterized by a half maximal concentration of c1/2=10 M TCNE. Simultaneously, TCNE inhibits the oxygen evolution rate of PS II membrane fragments with c1/2 3 M. 3.) The photoproduction of O2 is coupled with H+-uptake. This effect is diminished by the addition of the O2 -trap cyt c(III). 4.) D1/D2/Cytb559-complexes and PS II membrane fragments deprived of the extrinsic proteins and manganese exhibit no SOD-activity but are capable of producing O2 in the light if a PS II electron donor is added.Based on these results the site(s) of light induced superoxide formation in PS II is (are) inferred to be located at the acceptor side. A part of the PS II donor side and Cyt b559 in its HP-form are proposed to provide an intrinsic superoxide dismutase (SOD) activity.Abbreviations ADRY acceleration of the deactivation reactions of the water-splitting system Y - ANT-2p 2-(3-chloro-4-trifluoromethyl)anilino-3,5-dinitrothiophene - BCP bromocresol purple - cyt cytochrome - Cyt c cytochrome c - DCIP 2,6-dichlorophenol-indophenol - DCMU 3-(3,4-dichlorophenyl)-1,1-dimethylurea - DEDTC Diethyldithiocarbamate - DMBQ 2,5-dimethyl-p-benzoquinone - DPC 1,5-diphenylcarbazide - FCCP carbonylcyanide-p-trifluoro/methoxy-phenylhydrazone - HP high potential - LP low potential - MES 2-(N-morpholino)ethanesulfonic acid - NADP nicotinamide adenine dinucleotide phosphate - SOD superoxide dismutase - TCNE tetracyane ethylene - TEMED N,N,N,N-tetramethylethylenediamine  相似文献   

17.
Rat peritoneal macrophages stimulated with lipopolysaccharide (LPS) and Phorbol myristate acetate (PMA) generated increased levels of superoxide anions (O2ú-) by 122% as compared to those stimulated with PMA alone. However, Nitric oxide (NO) synthase inhibitors-n-monomethyl arginine (nMMA) or spermine-HCI lowered the enhanced levels of O2ú- released by LPS treated macrophages. The Superoxide dismutase (SOD) activity in LPS treated macrophages was 51% lower than that observed in resident cells. NO synthase inhibitors prevented the loss of SOD activity in LPS treated cells. Exogenously added SOD during sensitization of cells with LPS also inactivated the enzyme. This inactivation of SOD is inhibited by Nitric oxide synthase inhibitors. PMA alone did not affect SOD activity. NO synthase inhibitors also did not affect PMA activated superoxide anion generation in macrophages. These studies indicate that nitric oxide generated by LPS treated macrophages can inactivate SOD activity.  相似文献   

18.
Neurodegenerative diseases belong to a larger group of protein misfolding disorders, known as proteinopathies. There is increasing experimental evidence implicating prion-like mechanisms in many common neurodegenerative disorders, including Alzheimer disease, Parkinson disease, the tauopathies, and amyotrophic lateral sclerosis (ALS), all of which feature the aberrant misfolding and aggregation of specific proteins. The prion paradigm provides a mechanism by which a mutant or wild-type protein can dominate pathogenesis through the initiation of self-propagating protein misfolding. ALS, a lethal disease characterized by progressive degeneration of motor neurons is understood as a classical proteinopathy; the disease is typified by the formation of inclusions consisting of aggregated protein within and around motor neurons that can contribute to neurotoxicity. It is well established that misfolded/oxidized SOD1 protein is highly toxic to motor neurons and plays a prominent role in the pathology of ALS. Recent work has identified propagated protein misfolding properties in both mutant and wild-type SOD1, which may provide the molecular basis for the clinically observed contiguous spread of the disease through the neuroaxis. In this review we examine the current state of knowledge regarding the prion-like properties of SOD1 and comment on its proposed mechanisms of intercellular transmission.  相似文献   

19.
Superoxide dismutase (SOD) from bovine erythrocytes was conjugated with sodium hyaluronate (HA) with a mean molecular weight of 106 to have greater anti-inflammatory activity in vivo. Amino groups of SOD were coupled with carboxyl groups in the hyaluronate molecule using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The HA-SOD conjugate was composed of 1.5 mol of SOD molecule per 1 mol of hyaluronate on the average, and retained 70% of the activity of unmodified SOD. The conjugate was essentially non-immunogenic in mice, and exhibited much higher anti-inflammatory activities than HA or SOD in models of inflammatory diseases such as ischemic oedema of the foot-pad in mice, carrageenin-induced pleurisy and adjuvant arthritis in rats. This revised version was published online in November 2006 with corrections to the Cover Date.  相似文献   

20.
Regulation of superoxide dismutase synthesis in Candida albicans   总被引:2,自引:0,他引:2  
The synthesis of superoxide dismutase [SOD: EC 1.15.1.1] in response to various cultural conditions was examined in Candida albicans, an opportunistic yeast which causes candidiasis in immunosuppressed patients. SOD plays an important role in protecting cells from the oxidative damage of superoxide radicals. Maximum SOD activity was found after 72 hrs of yeast growth. The optimum pH and temperature for the SOD activity were 7 and 40 °, respectively. The major SOD activity was found in the cytosol fraction and the level of extracellular SOD was very low. The enzyme was stimulated to varying degrees by cholic acid, procaine and tocopherol. On the basis of inhibitor studies and other enzyme properties, the isolated enzyme from C. albicans is identified as copper and zinc superoxide dismutase. This revised version was published online in June 2006 with corrections to the Cover Date.  相似文献   

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