Plasma Extracellular Superoxide Dismutase Research Articles

Allele-Specific Effects on Extracellular Superoxide Dismutase Synthesis and Secretion

Plasma extracellular superoxide dismutase (ecSOD) concentrations are significantly (2 - 3-fold) higher in 129 mice than in the C57 strain. We reported earlier that the 129 strain carries a different allele of this enzyme, characterized by two amino acid substitutions and a 10 bp deletion in the 3’UTR of the mRNA. One of the substitutions is at the signal peptide cleavage site (position 21) while the other is within the catalytic site. Since the differences in plasma enzyme concentrations persist in congenic mice expressing the different alleles, the differences in plasma concentrations appear to be largely allele-driven and independent of the remainder of the genome. As expected, in vitro translation using rabbit reticulocyte lysate showed no differences in translational efficiency of transcripts and processing of the newly synthesized enzymes. Determinations of the rates of synthesis and secretion of the two isoforms of this enzyme in stably transfected CHO cells clearly demonstrate that the mature 129 variant is synthesized at rates nearly twice those of the wild-type isoform and has an intracellular pool size twice as large. However, both isoforms are secreted at the same fractional rate and have identical intracellular T1/2 as well as similar extent of degradation. These data explain, at least partially, the higher levels of ecSOD in congenic mice expressing the 129 variant, as well as enzyme levels in the 129 strain of mice. In silico calculations support this conclusion and indicate that the aa change at the signal peptide cleavage site (N21D) results in a substantial increase in cleavage probability at this site for the 129 variant. Our results also highlight the importance of signal peptide cleavage in determining steady-state levels of secretory proteins.

Effects of Medium Molecular Weight Heparinyl Phenylalnine on Superoxide Dismutase Activity in Mice.

We investigated the radical scavenging ability of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF) and medium molecular weight heparinyl leucine (MHL) in the blood of mice. The extracellular superoxide dismutase (EC-SOD) activity was measured according to the method by Oyanagui and Sato. As a result, HE significantly increased the EC-SOD activity with a significant prolongation of activated partial thromboplastin time (APTT), while MHF and MHL significantly increased the EC-SOD activity without a prolongation of APTT. Dose-response curve at 20 min after the injection of each compound indicated a bell-shape. Changes in the plasma EC-SOD activity of mice after the administration of HE, MHF and MHL (10 mg/kg/10 ml) were investigated time-dependently. The plasma EC-SOD activity peaked at 5 min after the administration of all compounds. These results indicated that MHF and MHL show a radical scavenging ability by increasing the EC-SOD activity and MHF may be a candidate for clinical use.

Effective microorganism – X attenuates circulating superoxide dismutase following an acute bout of intermittent running in hot, humid conditions

This study determined the effectiveness of antioxidant supplementation on high-intensity exercise-heat stress. Six males completed a high-intensity running protocol twice in temperate conditions (TEMP; 20.4°C), and twice in hot conditions (HOT; 34.7°C). Trials were completed following7 days supplementation with 70 ml·day−1 effective microorganism-X (EM-X; TEMPEMX or HOTEMX) or placebo (TEMPPLA or HOTPLA). Plasma extracellular Hsp72 (eHsp72) and superoxide dismutase (SOD) were measured by ELISA. eHsp72 and SOD increased pre-post exercise (p < 0.001), with greater eHsp72 (p < 0.001) increases observed in HOT (+1.5 ng·ml−1) compared to TEMP (+0.8 ng·ml−1). EM-X did not influence eHsp72 (p > 0.05). Greater (p < 0.001) SOD increases were observed in HOT (+0.22 U·ml−1) versus TEMP (+0.10 U·ml−1) with SOD reduced in HOTEMX versus HOTPLA (p = 0.001). Physiological and perceptual responses were all greater (p < 0.001) in HOT versus TEMP conditions, with no difference followed EM-X (p > 0.05). EM-X supplementation attenuated the SOD increases following HOT, potentiating its application as an ergogenic aid to ameliorate oxidative stress.

Exendin-4 induces extracellular-superoxide dismutase through histone H3 acetylation in human retinal endothelial cells.

Extracellular-superoxide dismutase (genetic name SOD3) is a secreted anti-oxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. Oxidative stress has been implicated in the pathogenesis of diabetic retinopathy; therefore, increases in extracellular-superoxide dismutase have been suggested to inhibit the progression of diabetic retinopathy. Incretin-based drugs such as glucagon-like peptide-1 receptor agonists are used in the treatment of type 2 diabetes. Glucagon-like peptide-1 receptor agonists are expected to function as extrapancreatic agents because the glucagon-like peptide-1 receptor is expressed not only in pancreatic tissues, but also in many other tissue types. We herein demonstrated that exendin-4, a glucagon-like peptide-1 receptor agonist, induced the expression of extracellular-superoxide dismutase in human retinal microvascular endothelial cells through epigenetic regulation. The results of the present study demonstrated that exendin-4 induced the expression of extracellular-superoxide dismutase through histone H3 acetylation at the SOD3 proximal promoter region. Moreover, plasma extracellular-superoxide dismutase concentrations in diabetic patients were elevated by incretin-based therapies. Therefore, incretin-based therapies may exert direct extrapancreatic effects in order to protect blood vessels by enhancing anti-oxidative activity.

Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes.

BackgroundOxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients.MethodsWe studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study (469 participants with type 1 diabetes at baseline; follow-up data for 259 participants), the GENESIS study (603 participants with type 1 diabetes at baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137 participants with type 2 diabetes at baseline and follow-up). Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants.ResultsIn GENEDIAB/GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29–0.78, p = 0.004) and the incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI 0.40–0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08–0.74, p = 0.004) and all-cause mortality (HR 0.44, 95% CI 0.21–0.73, p = 0.0006). The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction (HR 0.75, 95% CI 0.59–0.94, p = 0.01) and all-cause mortality (HR 0.87, 95% CI 0.79–0.97, p = 0.008) in DIABHYCAR.ConclusionsThe T-allele of rs2284659 in the promoter of SOD3 was associated with a more favorable plasma redox status and with better cardiovascular outcomes in diabetic patients. Our results suggest that EC-SOD plays an important role in the mechanisms of vascular protection against diabetes-related oxidative stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-014-0163-2) contains supplementary material, which is available to authorized users.

350 - Role of Plasma Extracellular Superoxide Dismutase during Malaria Infection in Ghanaian Children

350 - Role of Plasma Extracellular Superoxide Dismutase during Malaria Infection in Ghanaian Children

Effect of endoplasmic reticulum (ER) stress inducer thapsigargin on the expression of extracellular-superoxide dismutase in mouse 3T3-L1 adipocytes

Endoplasmic reticulum stress is related to metabolic disorders, including atherosclerosis and type 2 diabetes. It is known that inflammatory adipocytokines and oxidative stress are increased, while anti-inflammatory adipocytokines such as adiponectin are decreased in adipocytes during above conditions. Extracellular-superoxide dismutase is an anti-inflammatory enzyme that protects cells from oxidative stress. Because plasma extracellular-superoxide dismutase levels in type 2 diabetes patients were inversely related to the body mass index and homeostasis model assessment-insulin resistance index, it is speculated that the regulation of extracellular-superoxide dismutase might lead to the suppression of metabolic disorders. Here, we observed the reduction of extracellular-superoxide dismutase and adiponectin in 3T3-L1 adipocytes treated with thapsigargin, an endoplasmic reticulum stress inducer. Interestingly, tunicamycin, another endoplasmic reticulum stress inducer, did not decrease the expression of extracellular-superoxide dismutase in spite of the induction of glucose regulated protein kinase 78 kDa, an endoplasmic reticulum stress marker. Moreover, eukaryotic translation initiation factor 2α signaling cascade plays a pivotal role in the reduction of extracellular-superoxide dismutase in 3T3-L1 adipocytes during endoplasmic reticulum stress conditions.

Abstract 9760: Plasma Levels of Nitric Oxide Metabolites Are Markedly Reduced In Normotensive Individuals With Electrocardiographically Determined Left Ventricular Hypertrophy

Objective: It has recently been revealed that normotensive subjects with electrocardiographically determined left ventricular hypertrophy (ECG-LVH) are at risk of multiple cardiovascular diseases, but the underlying mechanism remains to be elucidated. To address this point, we examined the hypothesis that normotensive individuals with ECG-LVH show reduced plasma levels of metabolites of nitric oxide (NO), a critical regulator of cardiovascular function. Methods: A total of 579 Japanese male workers (40-65 years of age) were studied. Since hypertension (blood pressure ≥140/90 mmHg) or medications could influence plasma NOx (NO metabolites, nitrite and nitrate), workers with such factors were excluded from the study. ECG-LVH was assessed by the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The subjects were categorized by quartiles of plasma NOx level, and a multivariate logistic regression analysis was conducted relating ECG-LVH to NOx quartiles after adjustment for potential confounders. Results: The mean levels of plasma NOx were markedly lower in individuals with ECG-LVH (n=73, 28.9±19.2 μ mol/l) than in those without (n=506, 42.5±31.2 μ mol/l) ( P &lt;0.0001). The multivariate-adjusted odd ratio for the presence of ECG-LVH compared with the forth quartile of NOx (≥51.9 μ mol/l) was 1.38 (95% CI 0.55-3.59) for the third (NOx 33.1-51.8 μ mol/l), 1.83 (0.76-4.64) for the second (NOx 21.3-33.0 μ mol/l) and 4.93 (2.31-11.47) for the first quartile (NOx ≤21.2 μ mol/l). Similar result was obtained when subjects were stratified by waist circumference. The mean levels of plasma extracellular superoxide dismutase (EC-SOD), a major antioxidant in the cardiovascular system, were comparable in individuals with and without ECG-LVH. On the other hand, plasma EC-SOD levels were significantly decreased with lower quartiles of NOx ( P &lt;0.01). Conclusion: This study demonstrated for the first time that plasma NOx levels are markedly reduced in normotensive individuals with ECG-LVH. These results indicate that disrupted NO production through the involvement of down-regulation of the antioxidant enzyme may explain, at least in part, the potential mechanism for increased cardiovascular risk in normotensive individuals with ECG-LVH.

Smoking and COPD increase sputum levels of extracellular superoxide dismutase

Extracellular superoxide dismutase (ECSOD) is the major superoxide-scavenging enzyme in the lung. Certain ECSOD polymorphisms are protective against COPD. We postulated that smokers and COPD subjects would have altered levels of ECSOD in the lung, airway secretions, and/or plasma. Lung tissue ECSOD was evaluated from nonsmokers, smokers, and subjects with mild to very severe COPD by Western blot, immunohistochemistry, and ELISA. ECSOD levels in plasma, bronchoalveolar lavage fluid (BALF), and induced-sputum supernatants were analyzed by ELISA and correlated with smoking history and disease status. Immunohistochemistry identified ECSOD in extracellular matrix around bronchioles, arteries, and alveolar walls, with decreases seen in the interstitium and vessels of severe COPD subjects using digital image analysis. Plasma ECSOD did not differ between COPD subjects and controls nor based on smoking status. ECSOD levels in induced sputum supernatants were elevated in current smokers and especially in COPD subjects compared to nonsmokers, whereas corresponding changes could not be seen in the BALF. ECSOD expression was reduced around vessels and bronchioles in COPD lungs. Substantial increases in sputum ECSOD in smokers and COPD is interpreted as an adaptive response to increased oxidative stress and may be a useful biomarker of disease activity in COPD.

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Endothelial dysfunction in essential hypertension is an independent predictor for future cardiovascular events. Although inhibition of the renin-angiotensin system (RAS) reportedly improves endothelial function through its effects on oxidative stress and inflammation, questions remain regarding the factors that are pivotal for improvement of endothelial function by RAS inhibition. We therefore performed a prospective, randomized crossover trial in which an angiotensin II type 1 receptor antagonist, olmesartan and calcium channel blocker, amlodipine, were compared in 31 essential hypertensive patients. Results showed that, although both treatments achieved comparable lowering of blood pressure (BP), olmesartan, but not amlodipine, significantly improved endothelial function as evaluated by flow-mediated vasodilation (FMD) in the brachial artery. Although no significant changes in diabetic and lipid parameters were observed with either drug, olmesartan slightly decreased estimated glomerular filtration rate, which, surprisingly, translated into decreased microalbuminuria. In a similar vein, olmesartan reduced serum C-reactive protein and increased urine antioxidant levels compared with baseline, and reduced urine 8-epi-prostaglandin F2α levels compared with both baseline and amlodipine. Finally, although overall changes in plasma extracellular superoxide dismutase (EC-SOD) levels were not modulated by either treatment, for olmesartan there was a positive correlation between changes in FMD and those in EC-SOD levels. In conclusion, olmesartan improved endothelial function in hypertensive patients independent of its BP-lowering effect, which was due, at least in part, to its antioxidative property. Therefore, olmesartan might provide a greater long-term benefit for hypertensive patients with impaired endothelial function than amlodipine.

Extracellular Superoxide Dismutase Activity and Plasma Malondialdehyde in Human Immunodeficiency Virus Subjects of Kano State as Surrogate Markers of Cd4 Status

This study looked at the profile of plasma extracellular superoxide dismutase (SOD3) activity, malondialdehyde (MDA) vis-à-vis that of CD4 counts in human immunodeficiency virus subjects in Kano State, Nigeria. The subjects for this study comprised twenty (20) non-HIV infected volunteers as control and one hundred (100) HIV infected subjects. Forty nine (49) infected patients have not been on treatment, while fifty one (51) were at various stages of treatment. There was a negative correlation between the serum malondialdehyde concentration and CD4 count (Pearson r=-0.68, p&lt;0.01). There was also a negative correlation between serum malondialdehyde concentration and extracellular superoxide dismutase activity ((Pearson r=-0.71, p&lt;0.01) and Vitamin A concentration (Pearson r=-0.75; p&lt;0.01). Conversely a positive correlation was observed between the CD4 counts in HIV infected patients and activity of extracellular superoxide dismutase (Pearson r=0.86, p&lt;0.01). Similarly there was a positive correlation between CD4 count and serum vitamin A concentration (Pearson r=0.89 p&lt;0.01). The possibility remains for using these indicators to monitor HIV patients not eligible for therapy in resource constrained facilities of our rural areas.

Relationship Between Plasma Carotenoids, Fruit and Vegetable Intake, and Plasma Extracellular Superoxide Dismutase Activity in Women: Different in Health and Disease?

Abstract Exogenous antioxidants may influence endogenous antioxidant enzyme activity. We observed in healthy women (n = 95) that higher plasma α-carotene, β-carotene, β-cryptoxanthin, sum of plasma carotenoids, and fruit and vegetable intake were associated with lower plasma extracellular-superoxide dismutase activity. In women with a history of cardiovascular disease, diabetes, or cancer (n = 62), we observed no associations. Our observation that plasma extracellular-superoxide dismutase activity was inversely associated with plasma carotenoids and fruit and vegetable intake in healthy women, but not in women with a history of cardiovascular disease, diabetes, or cancer, suggests that the associations between exogenous and endogenous antioxidants may differ in health and disease.

The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis

In this study, we show that human extracellular superoxide dismutase (EC-SOD) binds to low-density lipoprotein receptor-related protein (LRP). This interaction is most likely responsible for the removal of EC-SOD from the blood circulation via LRP expressed in liver tissue. The receptor recognition site was located within the extracellular matrix-binding region of EC-SOD. This region encompasses the naturally occurring Arg213Gly amino acid substitution, which affects the affinity of EC-SOD for ligands in the extracellular space. Interestingly, the binding between LRP and Arg213Gly EC-SOD was significantly reduced, thus clarifying the observation that hetero- or homozygous carriers present with a significant increase in EC-SOD in their blood. On the basis of our results, we speculate that EC-SOD synthesized locally in tissues diffuses slowly into the circulation, from where it is removed by binding to LRP present in the liver. The interaction between LRP and EC-SOD is thus likely to be important for maintaining redox balance in the circulation.

The effect of hypoxia mimetic cobalt chloride on the expression of EC-SOD in 3T3-L1 adipocytes

It is well known that adipose tissue is not only a passive reservoir for energy storage but also produces and secretes a variety of bioactive molecules called adipocytokines, including adiponectin and tumor necrosis factor-α (TNF-α). Recently, it has been reported that adipose tissue can suffer a chronic hypoxic condition during hypertrophy of adipocytes, and this condition leads to the dysregulation of adipocytokines. Further, hypoxic adipocytes are in an increased oxidative stress. Extracellular-superoxide dismutase (EC-SOD) is an anti-inflammatory enzyme that protects cells from reactive oxygen species (ROS) by scavenging superoxide anion. Previous reports showed that plasma EC-SOD levels in type 2 diabetes patients were significantly and inversely related to the body mass index, homeostasis model assessment-insulin resistance index; however, the mechanisms of EC-SOD and adiponectin reductions during hypoxia remain poorly understood. Here, we demonstrate that cobalt chloride (CoCl2), a hypoxia mimetic, decreases EC-SOD and adiponectin in 3T3-L1 adipocytes by intracellular ROS-independent, but TNF-α and c-jun N-terminal kinase (JNK)-dependent mechanisms. From these results, it is possible that TNF-α is a key regulator of the reduction of EC-SOD and adiponectin in CoCl2-treated 3T3-L1 adipocytes, and we speculated that the reduction of EC-SOD and adiponectin would lead to and/or promote metabolic disorders.

Dietary fatty acid composition alters magnesium metabolism, distribution, and marginal deficiency response in rats*

Based on dietary intake recommendations, magnesium deficiency commonly occurs throughout the world. However, widespread pathological conditions induced by dietary magnesium deficiency have not been identified. This discrepancy may be caused by other dietary factors ameliorating or exacerbating the response to a marginal magnesium deficiency and/or the length of the deficiency. Thus, a study was performed to determine whether the n-6/n-3 fatty acid composition of the diet affects the response to marginal magnesium deprivation, and whether the effect was dependent upon the length of deprivation. Weanling female rats were fed diets containing 250 mg/kg magnesium in a factorial arrangement with dietary variables of supplemental magnesium at 0 or 250 mg/kg (total of 250 or 500 mg/kg) and fat sources of 75 g/kg corn oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 8 and 12 weeks on their respective diets, each rat was placed in a metabolic cage for a 16-hour collection of urine. After 13 weeks, the rats were anesthetized with ether for the collection of plasma and organs. Marginal magnesium deficiency was confirmed by decreased urinary excretion and femur, tibia and vertebrae concentrations of magnesium. Dietary oil influenced the effect of marginal magnesium deficiency on magnesium metabolism, distribution and oxidative stress indicators. Fish oil, but not corn oil, significantly decreased urinary magnesium excretion and increased kidney magnesium concentration. Femur magnesium was significantly decreased by marginal magnesium deficiency in rats fed fish oil but not in rats fed corn oil, and liver magnesium concentration was decreased by fish oil. Marginal magnesium deficiency increased plasma extracellular superoxide dismutase and cysteine (component of glutathione) in rats fed corn oil but not in rats fed fish oil. Urinary prostaglandin E₂ excretion was significantly decreased by marginal magnesium deficiency at 8 weeks, but not at 12 weeks; an increase between weeks 8 and 12 in marginally magnesium-deficient rats fed fish oil caused this change in significance. The findings show that the dietary fatty acid composition affects the response of rats to marginal magnesium deprivation. The findings also indicate that dietary or physiological factors affecting oxidative stress could affect the response to marginal magnesium deficiency, and that a response to a dietary change that takes time to develop, such as an increase in dietary n-3 fatty acids, may result in signs of marginal deficiency being different over time.

Expression of extracellular superoxide dismutase during adipose differentiation in 3T3-L1 cells

Obesity is known to be the primary causal component in metabolic syndrome. Adipocytes in obese patients exhibit increased oxidative stress via the activation of reactive oxygen species (ROS)-producing systems and inactivation of antioxidant enzymes. Extracellular superoxide dismutase (EC-SOD) is an anti-inflammatory enzyme that protects cells from the damaging effects of ROS. An earlier report showed that plasma EC-SOD levels in type 2 diabetic patients were significantly and inversely related to body mass index and homeostasis model assessment-insulin resistance index. Moreover, the administration of pioglitazone, an antidiabetic agent, significantly increased the plasma level of EC-SOD. In this report, the expression of EC-SOD was compared to other adipocytokines in mice 3T3-L1 pre-adipocytes. EC-SOD expression levels were increased after the induction of differentiation and then declined, which was similar to adiponectin and transcription factors such as peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein-α (C/EBP-α). On the other hand, the expression levels of pro-inflammatory adipocytokines, such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), increased markedly in the development stage of cells. It was observed that the expression of EC-SOD in differentiated 3T3-L1 cells co-cultured with LPS-stimulated J774 macrophages was up-regulated, while the addition of TNF-α down-regulated EC-SOD and adiponectin expression in adipocytes. It is known that infiltrated and activated macrophages produce extracellular ROS at high levels in adipose tissue. It is possible that the expression of EC-SOD in adipocytes was stimulated to protect them from oxidative stress in the co-culture system.

A combined marginal deficiency of copper and zinc does not exacerbate oxidant stress associated with copper or zinc deficiency

Both copper deficiency (Cu‐def) and zinc deficiency (Zn‐def) result in oxidative stress. Thus, an experiment was conducted to determine whether a marginal Zn‐def amplified oxidative stress responses to a marginal Cu‐def, or vice versa. Weanling male Sprague‐Dawley rats were assigned to groups of 10 and fed an AIN‐93G diet with dried egg whites as the protein source and modified to increase oxidative stress (safflower oil instead of soybean oil and sucrose instead of dextrinized cornstarch) for 6 wk. Dietary variables were the basal diet containing (per kg) 1.5 mg Cu and 8 mg Zn, and basal diet supplemented (per kg) with 4.5 mg Cu, 10 mg Zn, or 4.5 mg Cu and 10 mg Zn. Two additional groups of 10 rats were fed the diets containing 18 mg Zn and 1.5 or 6 mg Cu per kg and pair‐fed with corresponding rats fed 8 mg Zn/kg diet. Cu‐def increased plasma extracellular superoxide dismutase and 8‐isoprostaglandin F2α (F2‐IsoP); the increases were amplified by pair feeding but not by Zn‐def. Zn‐def did not exacerbate the Cu def‐induced decrease in plasma ceruloplasmin. Zn‐def decreased urinary F2‐IsoP in Cu‐def but not Cu‐adequate rats, and decreased plasma RANKL in Cu‐adequate but not Cu‐def rats. The dietary treatments did not affect urinary nitrate. The findings indicate that a combined marginal Cu‐def and Zn‐def did not exacerbate, and even alleviated, some signs (RANKL and F2‐IsoP) of oxidative stress.

Reduction in extracellular superoxide dismutase activity in African-American patients with hypertension

Superoxide anions react with nitric oxide to form peroxynitrite and hence reduce the bioavailability of nitric oxide in the arteries. Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger in human plasma and vascular tissues. The objective of this study is to assess whether essential hypertension is associated with an alteration in EC-SOD activity. In this report, blood samples were obtained from hypertensive ( n = 39) and normotensive ( n = 37) African-Americans. Plasma EC-SOD activity was measured using in-gel activity staining and spectrophotometric assays, EC-SOD protein level was measured using Western blotting, nitrotyrosine was measured using slot blotting, 8-isoprostane was measured with an enzyme immunoassay, and plasma copper and zinc concentrations were measured using an atomic absorption assay. Our data demonstrate that the copper, zinc, and plasma EC-SOD protein concentrations in the hypertensive and normotensive subjects are indistinguishable. Compared to normotensive controls, hypertensive patients have significantly reduced plasma EC-SOD activity. Plasma nitrotyrosine and 8-isoprostane levels are significantly higher in the hypertensive patients than in normotensive controls. Results from this study suggest that a reduction in EC-SOD activity in hypertensive patients is not due to a down-regulation of the SOD3 gene (encoding EC-SOD) or deficiency in mineral cofactors. Furthermore, the reduced EC-SOD activity might be at least partially responsible for the increased oxidative stress, as reflected by increased plasma nitrotyrosine and 8-isoprostane, in hypertensive subjects.

Decreased plasma extracellular superoxide dismutase level in patients with vasospastic angina

Objective Extracellular superoxide dismutase (EC-SOD) is the major extracellular scavenger of superoxides, and one of the main regulators of nitric oxide bioactivity in vessel walls. Here, we examined whether plasma EC-SOD level was associated with vasospastic angina (VSA), and if it was a risk factor for VSA. Methods and results We assigned 105 patients with normal or mildly stenotic coronary arteries into either a VSA ( n = 58) or chest pain syndrome (CPS) ( n = 47) groups. Plasma EC-SOD and other biochemical variables were measured, and major coronary risk factors were assessed. Results showed that apart from smoking status there were no significant differences in patient characteristics and biochemical variables between the two groups. In the VSA group, prevalence of smoking was significantly higher (53% versus 26%, p = 0.0055), and plasma EC-SOD level was significantly lower (68.9 ± 18.5 ng/ml versus 83.8 ± 25.9 ng/ml; p = 0.0009). Not only smoking (OR 2.742, 95% CI 1.032–7.287, p = 0.0431) but also plasma EC-SOD (OR 0.971, 95% CI 0.949–0.993, p = 0.0102) was an independent risk factor for VSA. Conclusions In patients with VSA, plasma EC-SOD level was substantially reduced. Furthermore, plasma EC-SOD level followed by cigarette smoking was the most predictive risk factor for coronary spasms.

Plasma Extracellular Superoxide Dismutase is Decreased in High-Altitude Mountaineers who are Endurance Trained

Restricted accessAbstractFirst published March 2006Plasma Extracellular Superoxide Dismutase is Decreased in High-Altitude Mountaineers who are Endurance TrainedE.A. Regan, R.P. Bowler, and J.D. CrapoView all authors and affiliationsVolume 54, Issue 2_supplhttps://doi.org/10.1177/108155890605402s137