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)

Oxidative stress is a constant threat to all living organisms and an immense repertoire of cellular defense systems is being employed by most pro- and eukaryotic systems to eliminate or to attenuate oxidative stress. Ischemia and reperfusion is characterized by both a significant oxidative stress and characteristic changes in the antioxidant defense. By focusing on this antioxidant response of the cardiovascular system in the setting of ischemia-reperfusion injury, the aim of this review was threefold. First, based on recent animal experiments and clinical studies we shall discuss how endogenous antioxidants respond to oxidative stress during ischemia-reperfusion injury and highlight the results of recent trials on the ability of antioxidants to modulate ischemia-reperfusion injury. In this aspect, we will particularly focus on the emerging concept that various lines of antioxidant defenses do not act individually but are linked to each other in a systematic relationship as part of an antioxidant network. It is well known that enzymatic mechanisms are important components of the endogenous antioxidant repertoire; however, the relative importance of the different enzyme systems and isoforms has been much debated. The second part will focus on recent suggestions attributing a potentially key role of mitochondrial MnSOD in cardiac ischemia-reperfusion injury. Finally, the third part of the review will critically examine how endogenous antioxidants might regulate the complex signal transduction pathways of cellular activation with particular attention to the NF-kappaB and MAPK systems that appears to determine outcome of injury, survival, and adaptation.
Arch Biochem Biophys 2003 Dec 15
PMID:Antioxidants in myocardial ischemia-reperfusion injury: therapeutic potential and basic mechanisms. 1465 61

The rotifer Brachionus plicatilis is a widely-used model for population dynamics studies. During the population growth of B. plicatilis, life history parameters such as reproduction and lifespan change widely, and determine the balance between birth and death rates that regulates the population fluctuations. The lifespan of B. plicatilis was extended 30% by inhibiting a phosphatidylinositol-3-OH kinase involved in an insulin/insulin-like growth factor (IGF) signal transduction pathway that regulates the reproduction and lifespan in nematodes. Subsequently, we cloned a cDNA encoding Mn-superoxide dismutase (SOD), which may function downstream of the IGF pathway. Real-time reverse-transcription polymerase chain reaction analysis revealed that the expression level of Mn-SOD mRNA was higher in B. plicatilis with longer lifespans than those with shorter lifespans. In addition, stress proteins may also influence population dynamics as molecules regulating lifespan and molecular chaperones to maintain the cellular integrity. Accordingly, we cloned two stress protein genes encoding HSP70 and GRP94, and found that their expression changed during the population growth of rotifers. Thus, this novel approach of integrating population ecology and molecular biology has potential use in investigation the detailed mechanisms of rotifer population dynamics.
Comp Biochem Physiol B Biochem Mol Biol 2003 Dec
PMID:The molecular mechanisms of life history alterations in a rotifer: a novel approach in population dynamics. 1466 96

Oxidative stress plays a key role in the development of microvascular complications of diabetes mellitus (DM). Antioxidant enzymes protect against the rapid onset of diabetic polyneuropathy (DPN) by reducing oxidative stress. Genetic variations that affect activity or expression levels of the antioxidant enzymes may therefore be associated with susceptibility to DPN. We examined polymorphic markers Ala(-9)Val in SOD2 gene and Arg213Gly in SOD3 gene for possible relation to DPN in Russian type 1 diabetic patients. Four hundred Russian white patients with type 1 diabetes were studied using neurological examination according to recommendations of the San Antonio Conference on Diabetic Neuropathy. Two groups were formed from the general sample. Definition of frequency distribution of the polymorphic markers was performed in these groups using the polymerase chain reaction. Genes encoding the enzymes Mn-SOD and extracellular superoxide dismutase (EC-SOD) were found to be associated with the pathogenesis of DPN.
Acta Diabetol 2003 Dec
PMID:Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study. 1470 72

Cortical spreading depression (CSD) is characterized by slowly propagating waves of neuronal/astrocytic depolarization and metabolic changes, followed by a period of quiescent neuronal and electroencephalographic activity. CSD acts as a preconditioning stimulus in brain, reducing cell death when elicited up to several days prior to an ischemic insult. Precise mechanisms associated with this neuroprotection are not known, although CSD increases the expression of a number of potentially neuroprotective genes/proteins. The nitric oxide (NO) system may be of particular importance, as it is acutely activated and chronically up-regulated in cerebral cortex by CSD, and NO can ameliorate and exacerbate cell death under different conditions. Several molecules have recently been identified that modulate the production and/or cellular actions of NO, but it is not known whether their expression is altered by CSD. Therefore, the present study examined the effect of CSD on the spatiotemporal expression of PIN, CAPON, PSD-95, Mn-SOD and Cu/Zn-SOD mRNA in the rat brain. In situ hybridization using specific [35S]-labelled oligonucleotides revealed that levels of PIN mRNA were significantly increased in the cortex and claustrum ( approximately 30-180%; p </= 0.01) after 6 h and 1 and 2 days, but were again equivalent to contralateral (control) cortical values at 7, 14 and 28 days. CAPON mRNA levels were increased ( approximately 30-180%; p </= 0.05) in the ipsilateral cortical hemisphere at 6 h and 2 days post treatment, but not at the other times examined. In contrast, levels of PSD-95, Mn- and Cu/Zn-SOD mRNA were not altered at any time after CSD. These results suggest that following CSD, nNOS activity and NO levels may be tightly regulated by both transcriptional and translational alterations in a range of nNOS adaptor proteins, which may contribute to CSD-induced neuroprotection against subsequent ischemia.
J Neurochem 2003 Dec
PMID:Neuronal-NOS adaptor protein expression after spreading depression: implications for NO production and ischemic tolerance. 1471 93

Pepper is a vegetable of importance in human nutrition. Currently, one of the most interesting properties of natural products is their antioxidant content. In this work, the purification and characterisation of peroxisomes from fruits of a higher plant was carried out, and their antioxidative enzymatic and non-enzymatic content was investigated. Green and red pepper fruits (Capsicum annuum L., type Lamuyo) were used in this study. The analysis by electron microscopy showed that peroxisomes from both types of fruits contained crystalline cores which varied in shape and size, and the presence of chloroplasts and chromoplasts in green and red pepper fruits, respectively, was confirmed. Peroxisomes were purified by differential and sucrose density-gradient centrifugations. In the peroxisomal fractions, the activity of the photorespiration, beta-oxidation and glyoxylate cycle enzymes, and the ROS-related enzymes catalase, superoxide dismutase, xanthine oxidase, glutathione reductase and NADP(+)-dehydrogenases, was determined. Most enzymes studied had higher specific activity and protein content in green than in red fruits. By native PAGE and western blot analysis, the localisation of a Mn-SOD in fruit peroxisomes was demonstrated. The ascorbate and glutathione levels were also determined in crude extracts and in peroxisomes purified from both green and red peppers. The total ascorbate content (200-220 mg per 100 g FW) was similar in crude extracts from the two types of fruits, but higher in peroxisomes from red peppers. The glutathione concentration was 2-fold greater in green pepper crude extracts than in red fruits, whereas peroxisomes from both tissues showed similar values. The presence in pepper peroxisomes of different antioxidative enzymes and their corresponding metabolites implies that these organelles might be an important pool of antioxidants in fruit cells, where these enzymes could also act as modulators of signal molecules (O2*-, H202) during fruit maturation.
J Plant Physiol 2003 Dec
PMID:Peroxisomes from pepper fruits (Capsicum annuum L.): purification, characterisation and antioxidant activity. 1471 45

Cytokines, phorbol esters, radiation and chemotherapeutic drugs up-regulate the expression of MnSOD (manganese superoxide dismutase). Using the VA-13 cell line, we studied the regulation of SOD2 upon treatment with PMA. Pre-treatment with CHX (cycloheximide) followed by PMA led to significantly higher levels of MnSOD mRNA compared with those with either agent alone, suggesting de novo synthesis of an inhibitory protein. PMA treatment modulates redox-sensitive transcription factors, therefore we evaluated the effects of this combination treatment upon AP-1 (activator protein 1) and NF-kappaB (nuclear factor kappaB), two trans-acting factors suggested to play a role in SOD2 regulation. Co-administration of CHX and PMA led to a time-dependent increase in the binding activity of NF-kappaB. Therefore we evaluated IkappaBalpha (inhibitory kappaBalpha) and found that co-administration decreased its steady-state level compared with either agent alone, suggesting that enhanced NF-kappaB activation is due to inhibition of IkappaBalpha synthesis. PMA activates PKC (protein kinase C) enzymes which phosphorylate IkappaBalpha, leading to its degradation, therefore we used GF109203X to inhibit PKC activity. Stable transfection utilizing a PMA-responsive element in the human SOD2 gene, showed a concentration-dependent decrease in luciferase and NF-kappaB-binding activity with GF109203X. Western blot analysis indicated the presence of several PKC isoforms in the VA-13 cell line; however, PMA pre-treatment specifically down-regulated alpha and betaI, suggesting a role for one or more of these proteins in SOD2 induction. Taken together, these results indicate that the PKC pathway leading to SOD2 induction proceeds at least in part through NF-kappaB and that inhibition of IkappaBalpha synthesis might serve as a potential pharmacological approach to up-regulate MnSOD.
Biochem J 2004 Dec 15
PMID:IkappaBalpha (inhibitory kappaBalpha) identified as labile repressor of MnSOD (manganese superoxide dismutase) expression. 1533 Jul 61

This study investigated the possibility that hyperglycemia induces early expression of various superoxide dismutases (SOD) and nitric oxide synthases (NOS) following focal cerebral ischemia in the rat. MnSOD, CuZnSOD, nNOS and eNOS mRNA and protein expression were examined 3 h after permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions. 2,3,5-triphenyltetrazolium chloride (TTC) treatment post-mortem revealed a significant area at risk of infarction following ischemia in hyperglycemic compared to normoglycemic rats. Although no changes in MnSOD, CuZnSOD, nNOS and eNOS mRNA expression were detected, Western blots of ischemic cortex revealed an increase in MnSOD and CuZnSOD protein expression in hyperglycemic compared to normoglycemic rats. Pre-treatment of hyperglycemic rats with the NOS inhibitors L-nitroarginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) or dehydroascorbic acid (DHA), a superoxide scavenger, significantly reduced the TTC delineated zone. The hyperglycemia-induced post-transcriptional upregulation of MnSOD and CuZnSOD levels suggest a response to increased superoxide production which, in the presence of increased nitric oxide production, may play a major role in the increased risk of damage following hyperglycemic stroke.
Neurochem Int 2004 Dec
PMID:Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat. 1538 Jun 26

Saccharomyces cerevisiae expresses two forms of superoxide dismutase (SOD): MnSOD, encoded by SOD2, which is located within the mitochondrial matrix, and CuZnSOD, encoded by SOD1, which is located in both the cytosol and the mitochondrial intermembrane space. Because two different SOD enzymes are located in the mitochondrion, we examined the relative roles of each in protecting mitochondria against oxidative stress. Using protein carbonylation as a measure of oxidative stress, we have found no correlation between overall levels of respiration and the level of oxidative mitochondrial protein damage in either wild type or sod mutant strains. Moreover, mitochondrial protein carbonylation levels in sod1, sod2, and sod1sod2 mutants are not elevated in cells harvested from mid-logarithmic and early stationary phases, suggesting that neither MnSOD nor CuZnSOD is required for protecting the majority of mitochondrial proteins from oxidative damage during these early phases of growth. During late stationary phase, mitochondrial protein carbonylation increases in all strains, particularly in sod1 and sod1sod2 mutants. By using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we have found that specific proteins become carbonylated in sod1 and sod2 mutants. We identified six mitochondrial protein spots representing five unique proteins that become carbonylated in a sod1 mutant and 19 mitochondrial protein spots representing 11 unique proteins that become carbonylated in a sod2 mutant. Although some of the same proteins are carbonylated in both mutants, other proteins are not. These findings indicate that MnSOD and CuZnSOD have both unique and overlapping functions in the mitochondrion.
J Biol Chem 2004 Dec 10
PMID:Mitochondrial protein oxidation in yeast mutants lacking manganese-(MnSOD) or copper- and zinc-containing superoxide dismutase (CuZnSOD): evidence that MnSOD and CuZnSOD have both unique and overlapping functions in protecting mitochondrial proteins from oxidative damage. 1538 44

Oxidative stress (OS) is thought to participate in the pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD). Excessive reactive oxygen species (ROS) production can occur during the normal aging process or following exposure to environmental toxicants. Dopamine neurons, which degenerate during PD, are particularly sensitive to oxidative stress. Polychlorinated biphenyls (PCBs), persistent and widespread pollutants, have been shown to adversely impact dopaminergic (DAergic) pathways, but the role ROS play in neurotoxicity remains unclear. To test the hypothesis that PCB exposure compromises dopamine neurons by stimulating ROS production, the direct toxicity and oxidative stress response following PCB exposure was examined both in MN9D dopamine cells and primary mesencephalic cultures. PCBs induced a time- and concentration-dependent increase in ROS production, which preceded cytotoxicity. Whereas intracellular GSH depletion exacerbated PCB effects, antioxidant pretreatment attenuated ROS production and cell death. Coincident alterations in antioxidant defense enzymes also accompanied ROS production, including decreased MnSOD and increased CuZnSOD protein levels. The robust elevation in heme oxygenase-1 levels further support the activation of oxidative stress mechanisms following PCB exposure. Furthermore, PCBs produced concentration-dependent reductions in intracellular dopamine levels and elevated dopamine turnover. Although the intracellular source of ROS remains unknown, these results suggest that sublethal PCB concentrations activate an oxidative stress-related pathway, which potentially disrupts dopamine neuron function.
Neurotoxicology 2004 Dec
PMID:Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. 1547 11

Ethanol consumption represents a major risk factor for cancer development, and a significant fraction of hepatocarcinomas arises in alcoholic liver cirrhosis. Increasing evidence indicates that ethanol acts as a tumor promoter on genetically initiated cells, by increasing the intracellular concentration of reactive oxygen species and promoting tissue necrosis/regeneration and cell proliferation. The tumor suppressor p53 restrains the expansion of carcinogen-initiated cells by inducing cell cycle arrest and apoptosis; accordingly, p53-deficient mice develop spontaneous and chemically induced neoplasms at a much higher frequency than normal mice. In normal mice exposed to a subacute (3 weeks) ethanol intoxication, a significant increase in the number of apoptotic hepatocytes was observed in concomitance with the up-regulation of the mitochondrial superoxide scavenger MnSOD, a reliable indicator of oxidative stress. Cell death occurred in the absence of liver inflammation and necrosis. Ethanol-induced hepatocyte apoptosis was completely abrogated in the p53 null background, suggesting that the tumor suppressor is necessary for hepatocyte death by ethanol. Accordingly, p53 -/- MEF were, unlike wild type cells, completely insensitive up to 0.5M ethanol in the culture medium. Strikingly, marked and widespread signs of dysplasia, with nuclear pleomorphisms and initial loss of normal architecture, heralding malignant transformation, were scored in all the mutant mice exposed to ethanol, but not in the control-fed littermates nor in ethanol-fed normal mice. These observations suggest that p53-dependent apoptosis restrains the tumorigenic effect of ethanol on liver cells, in agreement with the frequent loss of p53 function in HCC, and reveal an unexpected carcinogenic potential of alcohol which appears to be independent from the induction of cirrhosis and hepatocyte regeneration.
Biochem Biophys Res Commun 2004 Dec 03
PMID:Abrogation of hepatocyte apoptosis and early appearance of liver dysplasia in ethanol-fed p53-deficient mice. 1552 6


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