scholarly journals Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1236
Author(s):  
Maxwell Mathias ◽  
Joann Taylor ◽  
Elizabeth Mendralla ◽  
Marta Perez

Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3−/− (KO) mice were placed in normoxia (21% FiO2, RA) or chronic hyperoxia (75% FiO2, O2) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O2 mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O2 mice. KO-O2 mice had increased total SOD activity and increased VEGF expression when compared to WT-O2 mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype.

2008 ◽  
Vol 74 (24) ◽  
pp. 7643-7653 ◽  
Author(s):  
Carina Schulte ◽  
Matthias Arenskötter ◽  
Mahmoud M. Berekaa ◽  
Quyen Arenskötter ◽  
Horst Priefert ◽  
...  

ABSTRACT Gordonia westfalica Kb1 and Gordonia polyisoprenivorans VH2 induce the formation of an extracellular superoxide dismutase (SOD) during poly(cis-1,4-isoprene) degradation. To investigate the function of this enzyme in G. polyisoprenivorans VH2, the sodA gene was disrupted. The mutants exhibited reduced growth in liquid mineral salt media containing poly(cis-1,4-isoprene) as the sole carbon and energy source, and no SOD activity was detectable in the supernatants of the cultures. Growth experiments revealed that SodA activity is required for optimal growth on poly(cis-1,4-isoprene), whereas this enzyme has no effect on aerobic growth in the presence of water-soluble substrates like succinate, acetate, and propionate. This was detected by activity staining, and proof of expression was by antibody detection of SOD. When SodA from G. westfalica Kb1 was heterologously expressed in the sodA sodB double mutant Escherichia coli QC779, the recombinant mutant exhibited increased resistance to paraquat, thereby indicating the functionality of the G. westfalica Kb1 SodA and indirectly protection of G. westfalica cells by SodA from oxidative damage. Both sodA from G. polyisoprenivorans VH2 and sodA from G. westfalica Kb1 coded for polypeptides comprising 209 amino acids and having approximately 90% and 70% identical amino acids, respectively, to the SodA from Mycobacterium smegmatis strain MC2 155 and Micrococcus luteus NCTC 2665. As revealed by activity staining experiments with the wild type and the disruption mutant of G. polyisoprenivorans, this bacterium harbors only one active SOD belonging to the manganese family. The N-terminal sequences of the extracellular SodA proteins of both Gordonia species showed no evidence of leader peptides for the mature proteins, like the intracellular SodA protein of G. polyisoprenivorans VH2, which was purified under native conditions from the cells. In G. westfalica Kb1 and G. polyisoprenivorans VH2, SodA probably provides protection against reactive oxygen intermediates which occur during degradation of poly(cis-1,4-isoprene).


1996 ◽  
Vol 317 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Tim D. OURY ◽  
James D. CRAPO ◽  
Zuzana VALNICKOVA ◽  
Jan J. ENGHILD

Studies examining the biochemical characteristics and pharmacological properties of extracellular superoxide dismutase (EC SOD) have been severely limited because of difficulties in purifying the enzyme. Recently EC SOD was found to exist in high concentrations in the arteries of most mammals examined and it is the predominant form of SOD activity in many arteries. We now describe a three-step, high-yield protocol for the purification of EC SOD from human aorta. In the first step, the high affinity of EC SOD for heparin is utilized to obtain a fraction in which EC SOD constitutes roughly 13% of the total protein compared with only 0.3% of that of the starting material. In addition, over 80% of the original EC SOD activity present in the aortic homogenate was retained after the first step of purification. EC SOD was further purified using a combination of cation- and anion-exchange chromatography. The overall yield of EC SOD from this purification procedure was 46%, with over 4 mg of EC SOD obtained from 230 g of aorta. Purified EC SOD was found to exist predominantly as a homotetramer composed of two disulphide-linked dimers. However, EC SOD was also found to form larger multimers when analysed by native PAGE. It was shown by urea denaturation that the formation of multimers increased the thermodynamic stability of the protein. Limited proteolysis of EC SOD suggested that there is one interchain disulphide bond covalently linking two subunits. This disulphide bond involves cysteine-219 and appears to link the heparin-binding domains of the two subunits.


2005 ◽  
Vol 289 (2) ◽  
pp. H525-H532 ◽  
Author(s):  
Shinichiro Iida ◽  
Yi Chu ◽  
Joseph Francis ◽  
Robert M. Weiss ◽  
Carol A. Gunnett ◽  
...  

Oxidative stress is associated with endothelial dysfunction in heart failure. The goals of this study were to determine whether 1) gene transfer of extracellular superoxide dismutase (ecSOD) reduces levels of superoxide and improves endothelial function in the aorta and mesenteric artery in rats with heart failure, and 2) the heparin-binding domain (HBD) of ecSOD, by which ecSOD binds to cells, is required for protective effects of ecSOD. Seven weeks after coronary ligation, in rats with heart failure and sham-operated rats, we injected adenoviral vectors intravenously that express ecSOD, ecSOD with deletion of the HBD (ecSODΔHBD), or a control vector. Four days after injection of viruses, responses to acetylcholine, ADP, and sodium nitroprusside were examined in rings of the aorta and mesenteric artery. ecSOD bound to endothelium and increased SOD activity in the aorta after gene transfer of ecSOD, not ecSODΔHBD. Gene transfer of ecSOD, but not ecSODΔHBD, reduced levels of superoxide and improved relaxation to acetylcholine and ADP in the aorta and mesenteric artery from rats with heart failure. Improvement of relaxation to acetylcholine in the mesenteric artery from rats with heart failure after gene transfer of ecSOD was mediated in part by hydrogen peroxide. The major finding of this study is that the HBD of ecSOD is necessary for protection against endothelial dysfunction in rats with heart failure. We speculate that a common gene variant in the HBD of ecSOD, which is a risk factor for ischemic heart disease, may be a risk factor for vascular maladaptation and endothelial dysfunction in heart failure.


1987 ◽  
Vol 242 (1) ◽  
pp. 55-59 ◽  
Author(s):  
K Karlsson ◽  
S L Marklund

Extracellular superoxide dismutase (SOD) has previously been shown to be the major SOD isoenzyme in extracellular fluids. Upon chromatography on heparin-Sepharose it was separated into three fractions: A, without affinity; B, with intermediate affinity; and C, with relatively strong heparin affinity. Intravenous injection of heparin leads to a prompt increase in plasma extracellular-superoxide-dismutase (EC-SOD) activity. Heparin induces no release of EC-SOD from blood cells, nor does it activate EC-SOD in plasma, indicating that the source of the released enzyme is the endothelial-cell surfaces. No distinct saturation could be demonstrated in a dose-response curve up to 200 i.u. of heparin per kg body weight, showing that the releasing potency of heparin is lower for EC-SOD than for previously investigated heparin-released factors. Chromatography of human plasma on heparin-Sepharose shows nearly equal amounts of EC-SOD fractions A, B and C. Heparin induces specifically the release of fraction C. The findings point to the existence of an equilibrium of EC-SOD fraction C between the plasma phase and endothelial-cell surfaces. The major part of EC-SOD in the vasculature seems to be located on endothelial-cell surfaces.


2021 ◽  
Author(s):  
Jakub Treml ◽  
Petra Šalamúnová ◽  
Jaroslav Hanuš ◽  
Jan Hošek

Our results have shown a positive effect of a mixture of GPs and curcumin on Nrf2/ARE activation. Also, there was an observable increase of the expression of superoxide dismutase 1 (by the mixture) and heme oxygenase 1 (by composites).


2000 ◽  
Vol 279 (5) ◽  
pp. L977-L984 ◽  
Author(s):  
Eva Nozik-Grayck ◽  
Christine S. Dieterle ◽  
Claude A. Piantadosi ◽  
Jan J. Enghild ◽  
Tim D. Oury

Extracellular superoxide dismutase (EC-SOD), the only known enzymatic scavenger of extracellular superoxide, may modulate reactions of nitric oxide (NO) in the lungs by preventing reactions between superoxide and NO. The regulation of EC-SOD has not been examined in developing lungs. We hypothesize that EC-SOD plays a pivotal role in the response to increased oxygen tension and NO in the neonatal lung. This study characterizes rabbit EC-SOD and investigates the developmental regulation of EC-SOD activity, protein expression, and localization. Purified rabbit EC-SOD was found to have several unique biochemical attributes distinct from EC-SOD in other species. Rabbit lung EC-SOD contains predominantly uncleaved subunits that do not form disulfide-linked dimers. The lack of intersubunit disulfide bonds may contribute to the decreased heparin affinity and lower EC-SOD content in rabbit lung. EC-SOD activity in rabbit lungs is low before birth and increases soon after gestation. In addition, the enzyme is localized intracellularly in preterm and term rabbit lungs. Secretion of active EC-SOD into the extracellular compartment increases with age. The changes in EC-SOD localization and activity have implications for the neonatal pulmonary response to oxidative stress and the biological activity of NO at birth.


1994 ◽  
Vol 298 (2) ◽  
pp. 347-352 ◽  
Author(s):  
P Strålin ◽  
S L Marklund

To determine the effect of oxidative stress on expression of extracellular superoxide dismutase (EC-SOD), CuZn-SOD and Mn-SOD, two fibroblast lines were exposed for periods of up to 4 days to a wide concentration range of oxidizing agents: xanthine oxidase plus hypoxanthine, paraquat, pyrogallol, alpha-naphthoflavone, hydroquinone, catechol, Fe2+ ions, Cu2+ ions, buthionine sulphoximine, diethylmaleate, t-butyl hydroperoxide, cumene hydroperoxide, selenite, citiolone and high oxygen partial pressure. The cell lines were cultured both under serum starvation and at a serum concentration that permitted growth. Under no condition was there any evidence of EC-SOD induction. Instead, the agents uniformly, dose-dependently and continuously reduced EC-SOD expression. We interpret the effect to be due to toxicity. Enhancement of the protection against oxidative stress by addition of CuZn-SOD, catalase and low concentrations of selenite did not influence the expression of any of the SOD isoenzymes. Removal of EC-SOD from cell surfaces by heparin also did not influence SOD expression. Mn-SOD was moderately induced by high doses of the first 11 oxidants. Apart from reduction at high toxic doses, there were no significant effects on the CuZn-SOD activity by any of the treatments. Thus EC-SOD, previously shown to be profoundly influenced by inflammatory cytokines, was not induced by its substrate or other oxidants. In a similar fashion, Mn-SOD, previously shown to be greatly induced and depressed by cytokines, was only moderately influenced by oxidants. We suggest that the regulation of these SOD isoenzymes in mammalian tissues primarily occurs in a manner co-ordinated by cytokines, rather than as a response of individual cells to oxidants.


Author(s):  
V.D. Shadrina ◽  
N.A. Vakhnina ◽  
E.R. Boyko

For an untrained organism, physical activity is physiologically stressful. The stress is accompanied by an increase in reactive oxygen intermediates. Their level in the cell is regulated by antioxidant enzymes. The aim of the paper to study the activity of superoxide dismutase (SOD), glutathione peroxidase (GP) and glucose-6-phosphate dehydrogenase (G-6-FDH) in erythrocytes under single physical load (FL) of different intensity. Materials and Methods. The authors tested male Wistar rats aged 3 months. The animals were divided into seven groups: vivarium control (VC); rats who were swimming for 60 minutes without added weight (moderate intensity load (MIL)); four groups participating in load-testing: low-intensity FL (LI) – swimming with a load of 2 % of body weight; high-intensity FL (HI) - swimming with a load of 8 %, 10 % and 15 % of body weight (HI8, HI10, HI15). Animals of the seventh group (OS) were in the shallows for 60 min without the opportunity to swim in order to induce oxidative stress without physical load. Results. In all groups, the authors observed a significant decrease in SOD activity and a significant increase in GP and G-6-FDH activity relative to VC. The greatest decrease in SOD activity was in the OS and MIL groups (by 36 % and 33.5 %, p<0.01). During load testing, MIL group demonstarted a decrease in SOD activity by 29 % (p<0.01), in HI groups - by 25%, 26% and 22 %, respectively (p<0.05). GP and G-6-FDH activity increased in all experimental groups (p<0.05), GP activity increased in OS group by 78 %, G-6-FDH activity increased in OS and MIL groups by 160 %. Conclusion. When exposed to a single physical load of varying intensity, there was a decrease in SOD activity and an increase in GP and G-6-FDH activity relative to control. There were no differences in SOD and G-6-FDH activity between groups of swimming rats. There was a tendency to GP activity increase depending on the load intensity. Keywords: superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, erythrocytes, physical load. Для нетренированного организма физическая нагрузка – это физиологический стресс, сопровождающийся увеличением активных форм кислорода, уровень которых в клетке регулируется ферментами – антиоксидантами. Цель – исследование активности супероксиддисмутазы (СОД), глутатионпероксидазы (ГП) и глюкозо-6-фосфатдегидрогеназы (Г-6-ФДГ) эритроцитов при воздействии однократной физической нагрузкой (ФН) разной интенсивности. Материалы и методы. Работа выполнена на трехмесячных самцах крыс линии Wistar. Животные разделены на семь групп: виварный контроль (ВК); плававшие 60 мин без дополнительного веса (нагрузка умеренной интенсивности (УН)); четыре группы участвующих в нагрузочном тестировании: низко интенсивная ФН (НИ) – плавание с грузом 2 % от массы тела, высоко интенсивная (ВИ) – плавание с грузом 8, 10 и 15 % от массы тела (ВИ8, ВИ10, ВИ15). Животные седьмой группы (ОС) в течение 60 мин находились на мелководье без возможности плавать, чтобы вызвать окислительный стресс без физической нагрузки. Результаты. Во всех группах наблюдалось значимое снижение активности СОД и значимое повышение активности ГП и Г-6-ФДГ относительно ВК. Наибольшее снижение активности СОД показано в группах ОС и УН (на 36 и 33,5 %, p<0,01). При нагрузочном тестировании в группе УН отмечалось снижение активности СОД на 29 % (p<0,01), в группах ВИ – на 25, 26 и 22 % соответственно (p<0,05). Активность ГП и Г-6-ФДГ повышена во всех экспериментальных группах (p<0,05), активность ГП повышена в группе ОС на 78 %, Г-6-ФДГ – в группах ОС и УН на 160 %. Выводы. При воздействии однократной физической нагрузкой разной интенсивности наблюдается снижение активности СОД и повышение активности ГП, Г-6-ФДГ относительно контроля. Не выявлены различия активности СОД и Г-6-ФДГ между группами плававших крыс; показана тенденция к повышению активности ГП в зависимости от интенсивности нагрузки. Ключевые слова: супероксиддисмутаза, глутатионпероксидаза, глюкозо-6-фосфатдегидрогеназа, эритроциты, физическая нагрузка.


2022 ◽  
Vol 8 ◽  
Author(s):  
Xiankang Fan ◽  
Xiefei Li ◽  
Tao Zhang ◽  
Yuxing Guo ◽  
Zihang Shi ◽  
...  

Superoxide dismutase (SOD) is an important antioxidant enzyme with different physiological functions, which can be used as a nutritional fortifier in food. Cereal-based fermented products are becoming popular worldwide. In this study, novel millet-based flavored yogurt enriched with SOD was developed. Lactiplantibacillus plantarum subsp. plantarum was screened, which manufactured SOD activity of 2476.21 ± 1.52 U g−1. The SOD content of millet yogurt was 19.827 ± 0.323 U mL−1, which was 63.01, 50.11, and 146.79% higher than that of Bright Dairy Yogurt 1911, Junlebao and Nanjing Weigang, respectively. Fifty-four volatile flavor substances and 22,571 non-volatile flavor substances were found in yogurt. Compared to traditional fermented yogurt, 37 non-volatile metabolites in yogurt with millet enzymatic fermentation broth were significantly upregulated, including 2-phenyl ethanol, hesperidin, N-acetylornithine and L-methionine, which were upregulated by 3169.6, 228.36, 271.22, and 55.67 times, respectively, thereby enriching the sensory and nutritional value of yogurt. Moreover, the manufacture of unpleasant volatile flavor substances was masked, making the product more compatible with consumers' tastes.


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