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)

Mg2+, Ca2+, Mn2+, Zn2+, and Cu content of neurons from chick embryo cortex cultivated in chemically defined serum free growth medium was determined by energy dispersive X-ray fluorescence and atomic absorption spectroscopy. The intracellular volume of cultured neurons was determined to be 2.73 microliters/mg. Intracellular Mn2+, Fe2+, Zn2+, and Cu2+ in the cultivated neurons were 100-200 times the concentrations in the growth medium: Mg2+ and Ca2+ were 0.9 and 1.7 mM respectively, around 20 fold higher than in growth medium. Mg2+, Fe2+, Cu2+ and Zn2+ concentrations in neurons were in the range of ca. 300-600 microM, approximately 2-3 times the values previously reported in glial cells; Ca2+ and Mn2+ content of the neurons were higher by 5 and 10 fold respectively compared to glial cells. In neurons, the subcellular distribution of Fe2+, Cu2+, and Mn2+ follows the rank order: cytosol greater than microsomes greater than mitochondria; for Zn2+ the distribution differs as following: cytosol greater than mitochondria greater than microsomes. Determination of the superoxide dismutase activities in the cultivated neurons indicated that the Mn2+ linked activity predominates whereas, the Cu-Zn dependent enzyme is dominant in glial cells. Enrichment of the culture medium with Mn2+ to 2.5 microM enhanced the Mn-SOD by approximately 33% but the Cu2+-Zn2+ enzyme activity was not modified. The high Mn2+ content, the capacity to accumulate Mn2+, and the predominancy of the Mn-SOD form observed in neurons is in accord with a fundamental functional role for this metal ion in this type of brain cells.
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PMID:Levels and sub-cellular distribution of physiologically important metal ions in neuronal cells cultured from chick embryo cerebral cortex. 323 9

1. Rainbow trout (Salmo gairdneri) of mean initial weight 15 g were given either a low-manganese or control diet containing 1.3 and 33 mg Mn/kg dry diet respectively. 2. Weight gains over a 24-week feeding period were the same for both groups of trout. 3. Hepatosomatic index, blood packed cell volume and haemoglobin concentration, plasma protein and the activities of aspartic aminotransferase (EC 2.6.1.1) and alanine aminotransferase (EC 2.6.1.2) were unaffected by dietary Mn intake. 4. Plasma potassium and iron levels were increased in the trout given the low-Mn diet. 5. The hepatic levels of magnesium, sodium, K, zinc, copper, Mn and phosphorus were significantly reduced in the fish given the low-Mn diet. 6. In those trout given the low-Mn diet the levels of Mn and calcium in the vertebral ash were significantly reduced. 7. The hepatic activity of Cu-Zu superoxide dismutase (EC 1.15.1.1; Cu-ZnSOD) and of Mn superoxide dismutase (EC1.15.1.1; MnSOD) in cardiac muscle and liver was reduced in the group of trout given the low-Mn diet. The fall in Cu-ZnSOD and MnSOD activities coincided with reduced tissue levels of their respective metal components.
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PMID:The effect of low dietary manganese intake on rainbow trout (Salmo gairdneri). 731 45

Although much evidence favors the concept that dilated cardiomyopathy could be a postviral disease, the actual prevalence and pathogenesis of viral heart disease in dilated cardiomyopathy has not been well explored, since the diagnosis of viral infection is still difficult. The recently developed polymerase chain reaction (PCR) has made it possible to amplify a few copies of viral genome and has shown that viral genomes persist long after viral infection. The PCR is a promising method for testing possible viral etiology. We have found that antiheart antibodies associated with a murine model of myocarditis increased the intracellular free Ca2+ concentration through the activation of Ca(2+)-permeable cation channels in isolated ventricular cells. Marked induction of Mn-SOD and Cu/Zn-SOD mRNA was found in the heart with viral myocarditis and oxygen radicals may play an important role in the pathogenesis of viral myocarditis. Our recent studies revealed an increase in the circulating cytokines in patients with acute myocarditis and cardiomyopathy and suggested that cytokines play some role in the pathogenesis of myocardial injury in these diseases. In our animal model of EMC virus myocarditis, plasma tumor necrosis factor (TNF)-alpha was elevated in the acute stage and exogenously administered anti TNF-alpha antibody improved the survival and myocardial lesion, suggesting the importance of TNF-alpha in the pathogenesis.
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PMID:[Detection of viral genomes in myocarditis]. 773 17

(-)-Deprenyl stereospecifically reduces neuronal death even after neurons have sustained seemingly lethal damage at concentrations too small to cause monoamine oxidase-B (MAO-B) inhibition. (-)-Deprenyl can also influence the process growth of some glial and neuronal populations and can reduce the concentrations of oxidative radicals in damaged cells at concentrations too small to inhibit MAO. In accord with the earlier work of others, we showed that (-)-deprenyl alters the expression of a number mRNAs or proteins in nerve and glial cells and that the alterations in gene expression/protein synthesis are the result of a selective action on transcription. The alterations in gene expression/protein synthesis are accompanied by a decrease in DNA fragmentation characteristic of apoptosis and the death of responsive cells. The onco-proteins Bcl-2 and Bax and the scavenger proteins Cu/Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) are among the 40-50 proteins whose synthesis is altered by (-)-deprenyl. Since mitochondrial ATP production depends on mitochondrial membrane potential (MMP) and mitochondrial failure has been shown to be one of the earliest events in apoptosis, we used confocal laser imaging techniques in living cells to show that the transcriptional changes induced by (-)-deprenyl are accompanied by a maintenance of mitochondrial membrane potential, a decrease in intramitochondrial calcium and a decrease in cytoplasmic oxidative radical levels. We therefore propose that (-)-deprenyl acts on gene expression to maintain mitochondrial function and to decrease cytoplasmic oxidative radical levels and thereby to reduce apoptosis. An understanding of the molecular steps by which (-)-deprenyl selectively alters transcription may contribute to the development of new therapies for neurodegenerative diseases.
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PMID:(-)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. 898 61

Apoptotic, rather than necrotic, nerve cell death now appears as likely to underlie a number of common neurological conditions including stroke, Alzheimer's disease, Parkinson's disease, hereditary retinal dystrophies and Amyotrophic Lateral Sclerosis. Apoptotic neuronal death is a delayed, multistep process and therefore offers a therapeutic opportunity if one or more of these steps can be interrupted or reversed. Research is beginning to show how specific macromolecules play a role in determining the apoptotic death process. We are particularly interested in the critical nature of gradual mitochondrial failure in the apoptotic process and propose that a maintenance of mitochondrial function through the pharmacological modulation of gene expression offers an opportunity for the effective treatment of some types of neurological dysfunction. Our research into the development of small diffusible molecules that reduce apoptosis has grown from studies of the irreversible MAO-B inhibitor (-)-deprenyl. (-)-Deprenyl can reduce neuronal death independently of MAO-B inhibition even after neurons have sustained seemingly lethal damage. (-)-Deprenyl can also influence the process outgrowth of some glial and neuronal populations and can reduce the concentrations of oxidative radicals in damaged cells at concentrations too small to inhibit MAO. In accord with earlier work of others, we showed that (-)-deprenyl alters the expression of a number of mRNAs or of proteins in nerve and glial cells and that the alterations in gene expression/protein synthesis are the result of a selective action on transcription. The alterations in gene expression/protein synthesis are accompanied by a decrease in DNA fragmentation characteristic of apoptosis and the death of responsive cells. The onco-proteins Bcl-2 and Bax and the scavenger proteins Cu/Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD-2) are among the 40-50 proteins whose synthesis is altered by (-)-deprenyl. Since mitochondrial membrane potential correlates with mitochondrial ATP production, we have used confocal laser imaging techniques in living cells to show that the transcriptional changes induced by (-)-deprenyl result in a maintenance of mitochondrial membrane potential, a decrease in intramitochondrial calcium and a decrease in cytoplasmic oxidative radical levels. We therefore propose that (-)-deprenyl acts on gene expression to maintain mitochondrial function and decrease cytoplasmic oxidative radical levels and thereby reduces apoptosis. An understanding of the molecular steps by which (-)-deprenyl selectively alters transcription may lead to the development of new therapies for neurodegenerative diseases.
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PMID:Apoptosis in neurodegenerative disorders: potential for therapy by modifying gene transcription. 926 33

In an attempt to understand the role of free radicals in the regulation of sympathetic neurotransmission, the in vitro secretion of noradrenaline (NA) from synaptosomal preparations of guinea-pig ileum was investigated. Release of endogenous NA was quantified by an electrochemical detection (HPLC-ECD). In the presence of superoxide dismutase (SOD) and catalase at concentrations sufficient to scavenge the free radicals, secretion of NA was attenuated in samples with stimulation of 4-aminopyrine (4-AP) or not (spontaneous release). However, inducing superoxide radicals via the reaction of hypoxanthine with xanthine oxidase failed to modify the secretion of NA, both the 4-AP-stimulated release and the spontaneous secretion. Then, free radicals were induced in synaptosomes using hypoxia-normoxia exposure. Secretion of NA was markedly increased in samples receiving this treatment in a calcium-dependent way because it was attenuated by the removal of calcium chloride from bathing medium. An increase of SOD activity, both Mn-SOD and Cu, Zn-SOD, was also obtained by this exposure. Changes of SOD activities in response to free radicals produced by hypoxia-normoxia exposure in ileal synaptosomes can thus be considered. In conclusion, these results suggest that free radicals are formed to involve in the regulation of sympathetic neurotransmission via an increase of calcium influx to enhance the NA release in guinea-pig ileum.
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PMID:The role of free radicals in the release of noradrenaline from myenteric nerve terminals of guinea-pig ileum. 940 15

The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu, Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils.
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PMID:The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats. 951 4

The mechanism whereby mutations in the presenilin-1 (PS-1) gene on chromosome 14 cause early-onset inherited Alzheimer's disease are unknown. We report that PC6 neural cells (a subclone of PC12 cells) expressing PS-1 mutations (M146V and L286V) exhibit increased superoxide production, nitrotyrosine accumulation, and membrane lipid peroxidation following exposure to amyloid beta-peptide 1-42 (Abeta). Mitochondrial calcium accumulation and membrane depolarization following exposure to Abeta were enhanced in cells expressing mutant PS-1. Overexpression of mitochondrial Mn-SOD greatly reduced superoxide production, nitrotyrosine formation, membrane lipid peroxidation, intramitochondrial calcium accumulation, and membrane depolarization following exposure to Abeta and conferred resistance to the apoptosis-enhancing action of the PS-1 mutations. Nitric oxide synthase inhibitors and the peroxynitrite scavenger uric acid blocked the apoptosis-enhancing action of PS-1 mutations. The data suggest pivotal roles for superoxide production and resulting peroxynitrite formation in the pathogenic mechanism of PS-1 mutations.
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PMID:Superoxide mediates the cell-death-enhancing action of presenilin-1 mutations. 1036 13

The cytokine tumor necrosis factor (TNF) is toxic to some mitotic cells, but protects cultured neurons from a variety of insults by mechanisms that are unclear. Pretreatment of neurons or astrocytes with TNF caused significant increases in MnSOD activity, and also significantly attenuated 3-nitropropionic acid (3-NP) induced superoxide accumulation and loss of mitochondrial transmembrane potential. In oligodendrocytes, however, MnSOD activity was not increased, and 3-NP toxicity was unaffected by TNF. Genetically engineered PC6 cells that overexpress MnSOD also were resistant to 3-NP-induced damage. TNF pretreatment and MnSOD overexpression prevented 3-NP induced apoptosis, and shifted the mode of death from necrosis to apoptosis in response to high levels of 3-NP. Mitochondria isolated from either MnSOD overexpressing PC6 cells or TNF-treated neurons maintained resistance to 3-NP-induced loss of transmembrane potential and calcium homeostasis, and showed attenuated release of caspase activators. Overall, these results indicate that MnSOD activity directly stabilizes mitochondrial transmembrane potential and calcium buffering ability, thereby increasing the threshold for lethal injury. Additional studies showed that levels of oxidative stress and striatal lesion size following 3-NP administration in vivo are increased in mice lacking TNF receptors.
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PMID:Anti-death properties of TNF against metabolic poisoning: mitochondrial stabilization by MnSOD. 1037 69

Cyclooxygenase-2 (COX-2) is an essential enzyme for prostaglandin synthesis from arachidonic acid, during which considerable amounts of superoxide are produced. During pathological conditions, superoxide and nitric oxide (NO) rapidly form peroxynitrite, a potent cytotoxin, causing symptoms referred to as oxidative stress response. Superoxide is controlled by enzymes such as manganese- or copper-zinc-dependent superoxide dismutase (Mn-SOD, CuZn-SOD), glutathione peroxidase (GPx) and antioxidants derived from heme oxygenase (HO) activity such as biliverdin and bilirubin. NO derives from 3 NO-synthases (NOS I-III) from which the calcium-dependent NOS-I and III are activated rapidly due to hyperexcitation. We studied the induction of COX-2 by immunohistochemistry at days 1, 2 and 5 following cortical photothrombosis in normal and MK-801 treated rats. The results showed a weak constitutive, neuronal expression of COX-2 in cortex and amygdala. Layers II+III contained considerably more COX-2 than infragranular layers. One and 2 days following injury COX-2 was highly upregulated in the supragranular layers of the whole injured hemisphere compared with sham-operated animals and compared to the contralateral unlesioned hemisphere, whereas at day 5 COX-2 levels had returned to baseline. MK-801 treatment caused a reduction in COX-2 upregulation at day one and by day 2 no significant differences between injured and contralateral hemisphere were measurable. COX-2 positive neurons were found in close association with NOS-I containing neurons and their fibers but were not colocalized. In addition, codistribution of COX-2 was found with HO-1, CuZn-SOD and GPx containing cells, whereas COX-2 was colocalized with HO-2 and/or MnSOD in cortical neurons.
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PMID:Unilateral upregulation of cyclooxygenase-2 following cerebral, cortical photothrombosis in the rat: suppression by MK-801 and co-distribution with enzymes involved in the oxidative stress cascade. 1111 8


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