Regulation of lung manganese superoxide dismutase:  species variation in response to lipopolysaccharide

Lipopolysaccharide (LPS) treatment increases survival of rats, but not of mice, during hyperoxia. Manganese superoxide dismutase (Mn SOD) in the lung plays a critical role in LPS-induced tolerance to hyperoxia in rats. Therefore, we now compared the response of lung Mn SOD with treatment of mice and rats with LPS. LPS treatment of rats increased Mn SOD activity and protein concentration, did not change its specific activity, increased Mn SOD mRNA concentration 35-fold, and elevated Mn SOD synthesis 50% without changing general protein synthesis. LPS treatment of mice did not alter any of these parameters except for a 16-fold increase in Mn SOD mRNA concentration. Mn SOD translational efficiency (synthesis/mRNA concentration) was diminished 93% in rat lung and 76% in mouse lung by treatment with LPS. However, the absolute translational efficiency was twofold higher in lungs of LPS-treated rats than in lungs of LPS-treated mice. The failure of LPS to raise Mn SOD activity in mouse lungs is due, at least in part, to a smaller increase in Mn SOD mRNA and lower translational efficiency in LPS-treated mice than in LPS-treated rats.

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Pertussis toxin alters the concentration and turnover of manganese superoxide dismutase in rat lung

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.271.6.l875 ◽

1996 ◽

Vol 271 (6) ◽

pp. L875-L879

Author(s):

A. Berkovich ◽

D. Massaro ◽

L. B. Clerch

Keyword(s):

Superoxide Dismutase ◽

Pertussis Toxin ◽

Manganese Superoxide Dismutase ◽

Specific Activity ◽

Oxygen Toxicity ◽

Translational Efficiency ◽

Sod Activity ◽

Manganese Superoxide ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins

Treatment of rats with pertussis toxin (PTX) decreases the activity of manganese superoxide dismutase (Mn-SOD) in the lung and results in oxygen toxicity in air (L. B. Clerch, G. Neithardt, U. Spencer, J. A. Melendez, G. D. Massaro, and D. Massaro. J. Clin. Invest. 93: 2482-2489, 1994). To examine aspects of the mechanism of the PTX-induced fall in Mn-SOD activity, we injected rats with PTX (50 micrograms/kg), killed the rats 72 h later, and measured the activity, concentration, specific activity, and turnover of Mn-SOD in the lung. Treatment with PTX caused an approximately 50% fall in Mn-SOD activity and Mn-SOD concentration but no change in Mn-SOD specific activity. PTX also caused an increase in Mn-SOD mRNA concentration, a fall in Mn-SOD synthesis, and an increase in the half-life of Mn-SOD and general proteins. We conclude the PTX-induced low concentration of Mn-SOD is due to a decrease of translational efficiency. We suggest that, under normoxic conditions, signal transduction via heterotrimeric guanine nucleotide binding proteins regulates the expression of Mn-SOD at the level of translation and Mn-SOD degradation.

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Rat lung antioxidant enzymes: differences in perinatal gene expression and regulation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1992.263.4.l466 ◽

1992 ◽

Vol 263 (4) ◽

pp. L466-L470 ◽

Cited By ~ 15

Author(s):

L. B. Clerch ◽

D. Massaro

Keyword(s):

Gene Expression ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Manganese Superoxide Dismutase ◽

Late Gestation ◽

Postnatal Exposure ◽

Sod Activity ◽

Copper Zinc Superoxide Dismutase ◽

Manganese Superoxide ◽

Copper Zinc

The lung activity of the antioxidant enzymes (AOEs) copper, zinc superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GP), but not manganese superoxide dismutase (Mn SOD), increases in rats during late gestation; the concentrations of Cu,Zn SOD mRNA and CAT mRNA also rise. During early postnatal exposure to > 95% O2, the lung activity of Cu,Zn SOD, CAT, and GP increases. We now show 1) the lung concentration of Mn SOD mRNA and GP mRNA does not increase in late gestation; 2) Mn SOD activity and the concentration of its mRNA and of GP mRNA increase during exposure of neonatal rats to > 95% O2; and 3) as previously shown for CAT mRNA, the increase in lung concentration of the mRNAs for Cu,Zn SOD, Mn SOD, and GP during early postnatal hyperoxia occurs with a 70–80% prolongation of the half-life of these mRNAs. We conclude that 1) in late gestation the level at which lung AOE gene expression is regulated differs among the enzymes, 2) the level at which lung AOE gene expression is regulated shortly after birth in response to > 95% O2 is uniform among the enzymes, and 3) the lung's AOE response to neonatal hyperoxia is not merely a step-up of its prenatal regulation but involves different regulatory mechanisms based on increased stability of AOE mRNAs

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Exercise Provides Direct Biphasic Cardioprotection via Manganese Superoxide Dismutase Activation

Journal of Experimental Medicine ◽

10.1084/jem.189.11.1699 ◽

1999 ◽

Vol 189 (11) ◽

pp. 1699-1706 ◽

Cited By ~ 229

Author(s):

Nobushige Yamashita ◽

Shiro Hoshida ◽

Kinya Otsu ◽

Michio Asahi ◽

Tsunehiko Kuzuya ◽

...

Keyword(s):

Superoxide Dismutase ◽

Neutralizing Antibodies ◽

Time Course ◽

Manganese Superoxide Dismutase ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Sod Activity ◽

Manganese Superoxide ◽

Tnf Α ◽

Exercise Induced

Epidemiologic investigations have shown that exercise reduces morbidity and mortality from coronary artery disease. In this study, using a rat model, we attempted to determine whether exercise can reduce ischemic injury to the heart and elucidate a mechanism for the cardioprotective effect of exercise. Results showed that exercise significantly reduced the magnitude of a myocardial infarction in biphasic manner. The time course for cardioprotection resembled that of the change in manganese superoxide dismutase (Mn-SOD) activity. The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size. We showed that the level of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) increased after exercise. The simultaneous administration of the neutralizing antibodies to the cytokines abolished the exercise-induced cardioprotection and the activation of Mn-SOD. Furthermore, TNF-α can mimic the biphasic pattern of cardioprotection and activation of Mn-SOD. An antioxidant completely abolished cardioprotection and the activation of Mn-SOD by exercise or the injection of TNF-α as well as exercise-induced increase in TNF-α and IL-1β. The production of reactive oxygen species and endogenous TNF-α and IL-1β induced by exercise leads to the activation of Mn-SOD, which plays major roles in the acquisition of biphasic cardioprotection against ischemia/reperfusion injury in rats.

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Inconsistency between manganese superoxide dismutase expression and its activity involved in the degeneration of recognition function induced by chronic aluminum overloading in mice

Human & Experimental Toxicology ◽

10.1177/0960327115577522 ◽

2015 ◽

Vol 35 (1) ◽

pp. 63-68 ◽

Cited By ~ 2

Author(s):

H-M Qiu ◽

J-X Yang ◽

Q-S Jiang ◽

D He ◽

Q-X Zhou

Keyword(s):

Superoxide Dismutase ◽

Learning And Memory ◽

Time Course ◽

Manganese Superoxide Dismutase ◽

Memory Function ◽

Sod Activity ◽

Passive Learning ◽

Manganese Superoxide ◽

Recognition Function ◽

Spatial Recognition

Manganese (Mn) superoxide dismutase (SOD) is mainly located in mitochondrial matrix and is responsible for scavenging about 80% free radicals from oxidative and phospharylative process in mitochondria. It was reported that the insufficiency of Mn SOD expression or activity was connected to the development of neurodegenerative diseases. In this article, we investigated the time course related to the changes of Mn SOD expression and its activity from mouse brain as well as the recognition dysfunction in chronic aluminum (Al) overloading mice. Aluminum gluconate solution (equal to Al 400 mg/kg) was given to mice once a day, 6 days per week for 12 weeks via intragastric gavage. The learning and memory function, malondialdehyde (MDA) level as well as expression and activity of Mn SOD in cortex were determined. It was found that function of passive learning and memory and spatial recognition decreased, MDA level and Mn SOD expression increased during the period of chronic Al loading, but the Mn SOD activity rose from the 4th week and then decreased from the 8th week in cortex in Al overloading mice compared with the control. The results indicated that the inconsistency between Mn SOD expression and its activity might contribute to the development of recognition dysfunction induced by chronic Al overload.

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Alpha 1-adrenergic stimulation induces cardiac tolerance to hypoxia via induction and activation of Mn-SOD

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1356 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1356-H1362 ◽

Cited By ~ 2

Author(s):

N. Yamashita ◽

M. Nishida ◽

S. Hoshida ◽

J. Igarashi ◽

M. Hori ◽

...

Keyword(s):

Superoxide Dismutase ◽

Creatine Kinase ◽

Cardiac Myocytes ◽

Total Protein ◽

Manganese Superoxide Dismutase ◽

Specific Activity ◽

Adrenergic Stimulation ◽

Sod Activity ◽

Manganese Superoxide ◽

Tolerance To Hypoxia

We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.

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Molecular cloning and characterization of the copper/zinc and manganese superoxide dismutase genes from the human parasiteClonorchis sinensis

Parasitology ◽

10.1017/s003118200400695x ◽

2005 ◽

Vol 130 (6) ◽

pp. 687-697 ◽

Cited By ~ 12

Author(s):

A. H. LI ◽

Y. KONG ◽

S. H. CHO ◽

H. W. LEE ◽

B. K. NA ◽

...

Keyword(s):

Superoxide Dismutase ◽

Manganese Superoxide Dismutase ◽

Mrna Level ◽

Clonorchis Sinensis ◽

Amino Acid Sequences ◽

Sod Activity ◽

Intronless Gene ◽

Copper Zinc Superoxide Dismutase ◽

Manganese Superoxide ◽

Copper Zinc

A copper/zinc superoxide dismutase (Cu/ZnSOD) gene and a manganese superoxide dismutase (MnSOD) gene of the human parasiteClonorchis sinensishave been cloned and their gene products functionally characterized. GenesCu/ZnSODandMnSODencode proteins of 16 kDa and 25·4 kDa, respectively. The deduced amino acid sequences of the two genes contained highly conserved residues required for activity and secondary structure formation of Cu/ZnSOD and MnSOD, respectively, and show up to 73·7% and 75·4% identities with their counterparts in other animals. The genomic DNA sequence analysis of Cu/ZnSOD gene revealed this as an intronless gene. Inhibitor studies with purified recombinant Cu/ZnSOD and MnSOD, both of which were functionally expressed inEscherichia coli, confirmed that they are copper/zinc and manganese-containing SOD, respectively. Immunoblots showed that bothC. sinensisCu/ZnSOD and MnSOD should be antigenic for humans, and both, especially theC. sinensisMnSOD, exhibit extensive cross-reactions with sera of patients infected by other trematodes or cestodes. RT-PCR and SOD activity staining of parasite lysates indicate that there are no significant differences in mRNA level or SOD activity for both species of SOD, indicating cytosolic Cu/ZnSOD and MnSOD might play a comparatively important role in theC. sinensisantioxidant system.

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Helicobacter pylori (HP)-positive gastric cancer tissues showed increased manganese superoxide dismutase (Mn-SOD) activity and mRNA expression

Gastroenterology ◽

10.1016/s0016-5085(98)82346-9 ◽

1998 ◽

Vol 114 ◽

pp. A577

Author(s):

YW Chang ◽

YH Rah ◽

YG Kim ◽

SH Dong ◽

HJ Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Superoxide Dismutase ◽

Helicobacter Pylori ◽

Mrna Expression ◽

Manganese Superoxide Dismutase ◽

Sod Activity ◽

Manganese Superoxide ◽

Cancer Tissues

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Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.6.h2516 ◽

2001 ◽

Vol 280 (6) ◽

pp. H2516-H2523 ◽

Cited By ~ 42

Author(s):

Michela Zanetti ◽

Jun'Ichi Sato ◽

Zvonimir S. Katusic ◽

Timothy O'Brien

Keyword(s):

Superoxide Dismutase ◽

Endothelial Dysfunction ◽

Gene Transfer ◽

Manganese Superoxide Dismutase ◽

Ex Vivo ◽

Rabbit Aorta ◽

Sod Activity ◽

Manganese Superoxide ◽

Diabetic Rabbit ◽

Copper Zinc

Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and DM rings were transduced ex vivo with Ad vectors encoding Mn SOD (AdMn SOD), CuZn SOD (AdCuZn SOD), β-galactosidase (Adβgal), or diluents. In the absence of gene transfer, SOD activity was significantly increased in DM aortas. Transgene expression in DM AdCuZn SOD and DM AdMn SOD-transduced vessels was confirmed by Western blot analysis and by increased SOD activity (DM AdCuZn SOD, 76.2 ± 9.3; DM AdMn SOD, 65.2 ± 4.8; P < 0.05 vs. DM Adβgal; 50.9 ± 4.4 U/mg protein). Superoxide production was increased in DM Adβgal-transduced aorta and relaxations to acetylcholine were impaired in these vessels. Gene transfer of CuZn SOD and Mn SOD corrected both of these defects. Thus Ad-mediated gene transfer CuZn and Mn SOD to the diabetic aorta improves endothelium-dependent relaxation.

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Manganese superoxide dismutase in Meloidogyne incognita isolates selected for virulence on Mi-1-carrying tomato: gene expression and enzyme activity

Nematology ◽

10.1163/15685411-00002762 ◽

2014 ◽

Vol 16 (3) ◽

pp. 249-257

Author(s):

Sergio Molinari ◽

Laura Rosso

Keyword(s):

Gene Expression ◽

Superoxide Dismutase ◽

Enzyme Activity ◽

Meloidogyne Incognita ◽

Manganese Superoxide Dismutase ◽

Sod Activity ◽

Root Knot Nematodes ◽

Adult Females ◽

Manganese Superoxide ◽

Wide Range

Root knot nematodes (Meloidogyne spp.) are important pests of a wide range of crops, including tomato. Resistance of tomato to root-knot nematodes is conferred by the single dominant gene Mi-1, which currently is present in all commercially available resistant tomato cultivars. However, several resistance-breaking populations are being collected worldwide. Two isolates coming from the same standard population of Meloidogyne incognita, one selected for virulence against Mi-1 (SM1) and the other left avirulent (avr1), have been used in this study. qRT-PCR was used to detect transcript levels of the manganese superoxide dismutase (Mn-SOD) gene from (a)virulent pre-parasitic second-stage juveniles (J2). Over-expression of the Mn-SOD gene was found in the virulent isolate compared with the avirulent counterpart. The enzyme activity of membrane-bound mitochondrial Mn-SOD was assayed in J2 and adult females as the fraction of total SOD activity insensitive to hydrogen peroxide (H2O2). J2 from SM1 showed about a two-fold higher enzyme activity than J2 from avr1; conversely, no difference was found when adult females were tested. Proteins of J2 extracts were separated by n-PAGE on special mini-gels and stained for SOD. One slow migrating and three fast migrating bands were stained. SOD activity of the slow migrating band was H2O2-insensitive and enriched by treatment with the detergent Triton X-100. J2 survival was monitored in suspensions provided or not provided with the cell oxygen radical generator paraquat, at high concentration. Virulent J2 responded to paraquat treatment by increasing life extension with respect to control conditions; by contrast, avirulent J2 suffered major mortality in the presence of paraquat. Mn-SOD gene expression is discussed in relation to nematode fitness in oxidative stresses and vir phenotype.

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