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

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.
 ...
PMID:Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats. 1077 63

Glutathione (L-gamma-glutamyl-L-cysteinylglycine, GSH), is a vital intra- and extracellular protective antioxidant. Glutathione is synthesized from its constituent amino acids by the sequential action of gamma-glutamylcysteine synthetase (gamma-GCS) and GSH synthetase. The rate-limiting enzyme in GSH synthesis is gamma-GCS. Gamma-GCS expression is modulated by oxidants, phenolic antioxidants, and inflammatory and anti-inflammatory agents in various mammalian cells. The intracellular GSH redox homeostasis is strictly regulated to govern cell metabolism and protect cells against oxidative stress. Growing evidence has suggested that cellular oxidative processes have a fundamental role in inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox-sensitive transcription factors such as NF-kappaB and AP-1, which differentially regulate the genes for proinflammatory mediators and protective antioxidant genes such as gamma-GCS, Mn-SOD, and heme oxygenase-1. The critical balance between the induction of proinflammatory mediators and antioxidant genes and the regulation of the levels of GSH in response to oxidative stress at the site of inflammation is not known. Knowledge of the mechanisms of redox GSH regulation and gene transcription in inflammation could lead to the development of novel therapies based on the pharmacological manipulation of the production of this important antioxidant in inflammation and injury. This FORUM article features the role of GSH levels in the regulation of transcription factors, whose activation and DNA binding leads to proinflammatory and antioxidant gene transcription. The potential role of thiol antioxidants as a therapeutic approach in inflammatory lung diseases is also discussed.
 ...
PMID:Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. 1092 59

Primary glial cultures are able to express the inducible isoform of nitric oxide synthase (i-NOS) upon stimulation by bacterial lipopolysaccharides (LPS) and gamma-interferon (gamma-IfN). Immunocytochemical studies revealed, that under our experimental conditions i-NOS is expressed exclusively by the microglial cells and not in the astrocytes. Nitric oxide (NO) formation represents an oxidative load for the microglial cells, as observed by the oxidation rate of the ROS- and peroxynitrite indicator dichloro-dihydrofluorescein (DCF-H) in these cells. However, cell viability was not affected by the nitric oxide formation, indicating some form of protection against the higher oxidative load. Upregulation of Mn-SOD in the mitochondria in the course of the induction of i-NOS and, compared to the astrocytes, higher GSH levels in the microglial cells probably explain the resistance of the cultures against nitrosative stress. Increased SOD-activities in the mitochondria could lower the superoxide concentration in this organelle and may prevent an oxidative and/or nitrosative damage via a decreased peroxynitrite formation. The higher GSH-levels in the microglial cells of unstimulated cultures represents a buffer which, under the conditions of i-NOS catalyzed NO-formation, prevents a decline of the microglial GSH-levels below that of the astrocytes.
 ...
PMID:Nitrosative stress in primary glial cultures after induction of the inducible isoform of nitric oxide synthase (i-NOS). 1096 32

Previous studies, conducted on experimental animals, have indicated that reactive oxygen species (ROS) are involved in the aging process. The objective of this work was to study the relationship between oxidative damage and human skeletal muscle aging, measuring the activity of the main antioxidant enzymes superoxide dismutase (total and MnSOD), glutathione peroxidase (GPx) and catalase in the skeletal muscle of men and women in the age groups: young (17-40 years), adult (41-65 years) and aged (66-91 years). We also measured glutathione and glutathione disulfide (GSH and GSSG) levels and the redox index; lipid peroxidation and protein carbonyl content. Total SOD activity was lower in the 66-91 year-old vs. the 17-40 year-old men; MnSOD activity was significantly greater in 66-91 year-old vs. 17-40 year-old women. GPx activity remained unchanged. The activity of catalase was lower in adults than in young men but higher in the aged. We observed no changes in GSH levels and significantly higher GSSG levels only in aged men vs. adult men, and a significant decrease in aged women vs. aged men. The protein carbonyl content increased significantly in the 41-65 and 66-91 year-old vs. the 17-40 year-old men. Finally, young women have lower lipid peroxidation levels than young men. Significantly higher lipid peroxidation levels were observed in aged men vs. both young and adult men, and the same trend was noticed for women. We conclude that oxidative damage may play a crucial role in the decline of functional activity in human skeletal muscle with normal aging in both sexes; and that men appear to be more subject to oxidative stress than women.
 ...
PMID:Age and sex differences in human skeletal muscle: role of reactive oxygen species. 1099 82

Dietary copper- and iron restriction was achieved by application of the whole milk diet to growing rats in the course of 50 days. Three distinct responses of cytosolic and mitochondrial aconitases as well as of antioxidant defense system (CuZnSOD, MnSOD, catalase and GSH) to the dietary copper- and iron deficiency were established in liver, kidney and heart from experimental rats. The results were discussed with a view to the participation of ROS-generating processes in copper- and iron-deficient state. Differences in oxidative stability of cytosolic and mitochondrial aconitase activity of both control and experimental rats were also found. The in vitro increased aconitase activity of cytosol and the unchanged one of mitochondria from liver upon exposure of preparations to air were proved in vivo upon dietary copper- and iron restriction. This finding was interpreted to suggest the existence of putative aconitase activity.
 ...
PMID:Effect of dietary copper and iron restriction on aconitase activity and antioxidant capacity of liver, kidney and heart from growing rats. 1114 Jan 69

Patients with Down's syndrome (DS) show elevated levels of copper, zinc-containing superoxide dismutase (SOD1) and appear to have increased lipid peroxidation and oxidative damage to DNA as well as elevated glutathione peroxidase activity. Increasing SOD1 levels by gene transfection in NT-2 and SK-N-MC cell lines also led to a rise in glutathione peroxidase activity, but this was nevertheless accompanied by decreased proliferation rates, increased lipid peroxidation and protein carbonyls, and a trend to a rise in 8-hydroxyguanine and protein-bound 3-nitrotyrosine. Transfection of these cell lines with DNA encoding two mutant SOD1 enzymes (G37R and G85R) associated with familial amyotrophic lateral sclerosis (FALS), produced similar, but more severe changes, i.e. even lower growth rates, higher lipid peroxidation, 3-nitrotyrosine and protein carbonyl levels, decreased GSH levels, raised GSSG levels and higher glutathione peroxidase activities. Since G85R has little SOD activity, these changes cannot be related to increased O(2)(-) scavenging. In no case was SOD2 (mitochondrial Mn-SOD) level altered. Our cellular systems reproduce many of the biochemical changes observed in patients with DS or ALS, and in transgenic mice overexpressing mutant SOD1. They also show the potentially deleterious effects of SOD1 overexpression on cellular proliferation, which may be relevant to abnormal development in DS.
 ...
PMID:Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis. 1118 15

Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of gamma-glutamylcysteine synthetase (gamma-GCS). The expression of transforming growth factor-beta1 (TGF-beta1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-beta1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM.
 ...
PMID:Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats. 1126

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.
 ...
PMID:The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues. 1133 37

The response of aerobically grown Escherichia coli cells to the cold shock induced by the rapid lowering of growth temperature from 37 to 20 degrees C was found to be basically the same as the oxidative stress response. The enhanced sensitivity of cells deficient in two superoxide dismutases, Mn-SOD and Fe-SOD, and the increased expression of the Mn-SOD gene, sodA, in response to cold stress were interpreted as both oxidative and cold stresses are due to a rise in the intracellular level of superoxide anion. The long-term cultivation of E. coli at 20 degrees C was also accompanied by the typical oxidative stress response reactions--an enhanced expression of the Mn-SOD and catalase HPI genes and a decrease in the intracellular level of reduced glutathione (GSH) and in the GSH/GSSG ratio.
 ...
PMID:[Role of the antioxidant system in response of Escherichia coli bacteria to cold stress]. 1133 38

The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague-Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg(-1), i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg(-1), i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg(-1), i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by approximately 50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and -dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas +/-dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, +/-dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis.
 ...
PMID:Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stress. 1143 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>