Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to provide data on the dose-dependent production of dicentrics and micronuclei in human lymphocytes irradiated with 22.6 MeV protons and to estimate the possible contribution of intracellular superoxide dismutases (SOD) to the relative biological effectiveness (RBE) of protons. For the dose-response study, heparinized whole blood of a healthy volunteer was irradiated with protons and X-rays employing radiation doses of 0.5-4 Gy. Three biological endpoints were analyzed: chromosomal aberrations, micronuclei, and specific activity of cytosolic (CuZnSOD) and mitochondrial (MnSOD) superoxide dismutases in harvested human blood cells. Dicentric dose-response curves fit a linear-quadratic form (alpha = 0.094 +/- 0.006, beta = 0.032 +/- 0.001) induced with X-rays and (alpha = 0.119 +/- 0.057, beta = 0.029 +/- 0.014) for 22.6 MeV protons. Protons were more effective than X-rays in producing exchanges, particularly at 0.5 and 1 Gy. In contrast to X-ray irradiated samples where a significant increase in the specific activity of MnSOD was recorded (up to a radiation dose of 1 Gy), irradiation with protons markedly reduced its activity. As a consequence of the reduced activity of MnSOD, the chromosomal dose-response curve became quadratic. The RBE for dicentrics varies with dose (from 2.2 to 1.01) and reduced activity of MnSOD is an important contributor to the RBE of protons. SODs, particularly MnSOD, play an important role in defending DNA from reactive oxygen species. A reduced activity of SOD, particularly MnSOD, is an important contributor to the RBE of protons.
Cell Mol Life Sci 2000 May
PMID:Chromosome aberrations, micronuclei, and activity of superoxide dismutases in human lymphocytes after irradiation in vitro. 1089 48

Superoxide (O2-) has been implicated in the pathogenesis of pulmonary O2 toxicity. The studies using transgenic and knockout mice of each of the three isoforms of superoxide dismutase (SOD) e.g. , CuZnSOD, MnSOD and extracellular SOD (EC-SOD), have demonstrated that O2- produced in the mitochondria from its electron transport system and extracellular O2- generated by infiltrating neutrophils, and possibly its derivatives e.g., hydroxyl radical and peroxynitrite, are important mediators of hyperoxia-induced pulmonary injury, while cytoplasmic O2- plays a limited, if any, role in the pathogenesis of pulmonary O2 toxicity. Distal airway epithelial cells including type II alveolar and non-ciliated bronchiolar epithelial cells, are important targets for O2 radicals under the hyperoxic condition. The accessibility of these distal airway epithelial cells to in vivo gene transfer through the tracheal route of administration, suggests the potential for in vivo transfer of MnSOD and EC-SOD genes as a future approach in the prevention of pulmonary O2 toxicity.
Int J Mol Med 2001 Jan
PMID:Superoxide dismutase and pulmonary oxygen toxicity: lessons from transgenic and knockout mice (Review). 1111 2

The aim of this study was to investigate the influence of acute cold exposure on the mRNA expression and immunoreactivity of superoxide dismutase (SOD) isoenzymes [Mn-SOD, Cu,Zn-SOD, and extracellular-SOD (EC-SOD)] in different tissues from lean and obese (ob/ob) mice at 10 months of age. The animals were kept at 10 degrees C for 3 h, with the colonic temperature in obese mice declining progressively during the cold stress, but not in lean mice, probably because of a strong tendency to atrophy of the brown adipose tissue (BAT) in obese mice. In the expression of mRNAs for lean mice, acute cold exposure led to a significant increase only in Mn-SOD in testes, but a significant decline in Cu,Zn-SOD in kidney and in Mn-SOD and EC-SOD in white adipose tissue (WAT), as well as in all SOD isoenzymes in lung and BAT. In obese mice, the mRNA level of Mn-SOD in heart and gastrocnemius muscle was significantly decreased following the cold exposure, whereas that of EC-SOD in testes was significantly increased. These changes, however, were not always accompanied by those in the corresponding protein levels; for example, the significant decreases in the expression of mRNAs for the three SOD isoenzymes in lung and BAT from lean mice did not result in any changes in the respective isoenzyme protein levels. These results suggest that, except for testes, a cold-exposure period of 3 h down-regulates SOD isoenzymes at the transcriptional process especially in lean mice, but is not long enough to induce their protein synthesis. It seems likely, thus, that, despite a marked decrease in colonic temperature, acute exposure to cold has less effect on SOD isoenzymes in obese mice as compared with those in normal lean siblings.
Res Commun Mol Pathol Pharmacol 1999
PMID:Effects of acute cold stress on mrna expression and immunoreactivity of three superoxide dismutase isoenzymes in genetically obese mice. 1112 8

Norepinephrine (NE) causes hypertrophic growth of cardiac myocytes via stimulation of alpha1-adrenergic receptors (alpha1-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate alpha1-AR-stimulated hypertrophic growth in adult rat ventricular myocytes (ARVM). NE increased the level of intracellular ROS as assessed by lucigenin chemiluminescence or cytochrome c reduction, and this effect was prevented by the superoxide dismutase (SOD)-mimetic MnTMPyP. NE also caused the induction of MnSOD mRNA. alpha1-AR stimulation with NE (1 microM) in the presence of propranolol (2 microM) for 48-96 h caused a hypertrophic growth phenotype characterized by a 36+/-3% increase in 3H-leucine incorporation, a 49+/-14% increase in protein accumulation, a six-fold induction of atrial natriuretic peptide mRNA, actin filament reorganization, and the induction of MnSOD mRNA. These responses were all prevented by pretreatment with the alpha1-AR-selective antagonist prazosin (100 n M) or the SOD-mimetics MnTMPyP (50 microM) and Euk-8 (100 microM). MnTMPyP had no effect on alpha1-AR-stimulated 3H-inositol phosphate turnover or the hypertrophic phenotype caused by the protein kinase C activator phorbol-12-myristate-13-acetate. Thus, ROS play a critical role in mediating the hypertrophic growth response to alpha1-AR-stimulation in ARVM.
J Mol Cell Cardiol 2001 Jan
PMID:Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. 1113 29

The sodA gene from Erwinia chrysanthemi strain 3937 was cloned by functional complementation of an Escherichia coli sodA sodB mutant and sequenced. We identified a 639-bp open reading frame, which encodes a protein that is 85% identical to the E. coli manganese-containing superoxide dismutase MnSOD. Promoter elements of this gene were identified by transcriptional mapping experiments. We constructed an E. chrysanthemi deltasodA mutant by reverse genetics. The deltasodA mutation resulted in the absence of a cytoplasmic SOD, which displays the same characteristics as those of MnSOD. The deltasodA mutant was more sensitive to paraquat than the wild-type strain. This mutant could macerate potato tubers, similar to the wild-type strain. In contrast, when inoculated on African violets, the mutant produced, at most, only small necrotic lesions. If the inoculum was supplemented with the superoxide anion-scavenging metalloporphyrin MnTMPyP or purified SOD and catalase, the deltasodA mutant was able to macerate the inoculated zone. Generation of superoxide anion by African violet leaves inoculated with E. chrysanthemi was demonstrated with nitroblue tetrazolium as an indicator. Therefore, at the onset of infection, E. chrysanthemi cells encounter an oxidative environment and require active protective systems against oxidative damages such as MnSOD to overcome these types of conditions.
Mol Plant Microbe Interact 2001 Jun
PMID:Essential role of superoxide dismutase on the pathogenicity of Erwinia chrysanthemi strain 3937. 1138 71

The effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and H2O2, on hepatitis B virus (HBV) replication was analyzed in the HBV DNA transfected human hepatoblastoma-derived cell line HB 611. Secretion of HBV DNA from HB611 cells was inhibited by IFN-gamma, TNF-alpha, IL-1beta, and H2O2 in a dose-dependent manner. These cytokines and H2O2 also decreased HBV mRNA expression in HB611 cells, meaning that these reagents decreased the synthesis of all virally encoded components of the HBV virion. The level of manganese-SOD mRNA, indicative of occurrence of oxidative stress, increased immediately after treatment with IFN-gamma, TNF-alpha, IL-1beta, and H2O2. Moreover, the antioxidant N-acetyl-L-cysteine substantially inhibited the antiviral effect. Our findings suggest that oxidative stress may be a common factor in the antiviral effects of IFN-gamma, TNF-alpha, and IL-1beta on HBV.
Res Commun Mol Pathol Pharmacol
PMID:Interferon-gamma, tumor necrosis factor-alpha, and interleukin 1-beta suppress the replication of hepatitis B virus through oxidative stress. 1158 67

The composition of antioxidant enzymes, especially superoxide dismutase (SOD), was studied in one nontransgenic and three transgenic lines of nodulated alfalfa plants. Transgenic lines overproduced MnSOD in the mitochondria of nodules and leaves (line 1-10), MnSOD in the chloroplasts (line 4-6), and FeSOD in the chloroplasts (line 10-7). In nodules of line 10-7, the absence of transgene-encoded FeSOD activity was due to a lack of mRNA, whereas in nodules of line 4-6 the absence of transgene-encoded MnSOD activity was due to enzyme inactivation or degradation. Transgenic alfalfa showed a novel compensatory effect in the activities of MnSOD (mitochondrial) and FeSOD (plastidic) in the leaves, which was not caused by changes in the mRNA levels. These findings imply that SOD activity in plant tissues and organelles is regulated, at least partially, at the posttranslational level. All four lines had low CuZnSOD activities and an abundant FeSOD isozyme, especially in nodules, indicating that FeSOD performs important antioxidant functions other than the scavenging of superoxide radicals generated in photosynthesis. This was confirmed by the detection of FeSOD cDNAs and proteins in nodules of other legumes such as cowpea, pea, and soybean. The cDNA encoding alfalfa nodule FeSOD was characterized and the deduced protein found to contain a plastid transit peptide. A comparison of sequences and other properties reveals that there are two types of FeSODs in nodules.
Mol Plant Microbe Interact 2001 Oct
PMID:Expression studies of superoxide dismutases in nodules and leaves of transgenic alfalfa reveal abundance of iron-containing isozymes, posttranslational regulation, and compensation of isozyme activities. 1160 57

The present study was undertaken to investigate the effect of tumour necrosis factor-alpha (TNFalpha) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNFalpha between ESC and decidualized ESC. TNFalpha increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNFalpha required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNFalpha had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNFalpha-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNFalpha-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNFalpha-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNFalpha effect. In summary, TNFalpha induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cytokine-mediated oxidative stress.
Mol Hum Reprod 2001 Nov
PMID:Induction of manganese superoxide dismutase by tumour necrosis factor-alpha in human endometrial stromal cells. 1167 73

Previous studies have demonstrated that preconditioning the brain with cortical spreading depression (CSD) induces tolerance to a subsequent episode of ischemia. In other models of preconditioning, induction of ischemic tolerance has been associated with increased expression of the antioxidant enzyme, superoxide dismutase (SOD). The objective of the present study was to determine whether CSD upregulates Cu/Zn-SOD or Mn-SOD. CSD was induced in one hemisphere by applying 2 M KCl to the frontal cortex in Wistar rats. After 2 or 24 h of recovery, Cu/Zn-SOD and Mn-SOD mRNA levels were determined in both hemispheres using Northern blot analysis. In separate rats, Cu/Zn-SOD and Mn-SOD protein levels were determined 24 and 72 h after CSD using Western blot analysis. In addition, total SOD, Cu/Zn-SOD and Mn-SOD enzymatic activities were measured 24 and 72 h after CSD using spectrophotometric and zymographic assays. At the times investigated, no significant differences in mRNA or protein levels for Cu/Zn-SOD or Mn-SOD were observed between the ipsilateral and contralateral cortex. Further, there were no significant differences in Cu/Zn-SOD or Mn-SOD enzymatic activities between the two hemispheres at 24 or 72 h after CSD. In addition, CSD did not alter the activities of Cu/Zn-SOD or Mn-SOD in either hemisphere, relative to those in unoperated animals. Taken together, these results fail to support the hypothesis that CSD-induced tolerance is mediated through the upregulation of Cu/Zn-SOD or Mn-SOD.
Brain Res Mol Brain Res 2001 Nov 30
PMID:Preconditioning with cortical spreading depression does not upregulate Cu/Zn-SOD or Mn-SOD in the cerebral cortex of rats. 1173 Oct 8

The present study was undertaken to investigate the role of estrogen and progesterone in the expression of copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in human endometrial stromal cells (ESC). ESC were incubated with estradiol (10(-8) mol/l), medroxyprogesterone acetate (MPA, 10(-6) mol/l), or estradiol + MPA for 18 days. MPA significantly increased Cu,Zn-SOD and Mn-SOD mRNA levels and enzyme activities as well as the mRNA level of insulin-like growth factor-binding protein-1 (IGFBP-1), a marker for decidualization. Estradiol only augmented the effects of MPA on Cu,Zn-SOD activity and IGFBP-1 mRNA level, and estradiol alone had no effect. To study the withdrawal of estrogen and progesterone (EP withdrawal), ESC that had been treated with estradiol + MPA for 12 days were washed and then incubated with or without estradiol + MPA for a further 11 days. Cu,Zn-SOD mRNA levels and activities declined after EP withdrawal, while they were gradually increased by the continuous treatment with estradiol + MPA. In contrast, Mn-SOD mRNA levels and activities were not affected by EP withdrawal. IGFBP-1 mRNA levels were significantly increased 4 days after EP withdrawal and decreased thereafter, whereas they were gradually increased by the continuous treatment with estradiol + MPA. In conclusion, Cu,Zn-SOD, Mn-SOD and IGFBP-1 are differently regulated by estrogen and progesterone in human ESC. The decrease in Cu,Zn-SOD after the ovarian steroid withdrawal may be involved in endometrial breakdown.
Mol Hum Reprod 2002 Jan
PMID:Differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone withdrawal in human endometrial stromal cells. 1175 71


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