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)

Many individuals with cardiac diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of physical training and chronic nitric oxide synthase (NOS) inhibitor (nitro-L-arginine methyl ester, L-NAME) treatment on blood pressure (BP), heart rate (HR) and cardiac oxidant/antioxidant systems in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control (SC), (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, s.c. for 8 weeks) and (4) ET+L-NAME. BP and HR were monitored with tail-cuff method. The animals were sacrificed 24 h after last treatments and hearts were isolated and analyzed. Physical conditioning significantly increased respiratory exchange ratio (RER), cardiac nitric oxide (NO) levels, NOS activity and endothelial (eNOS) and inducible (iNOS) protein expression. Training significantly enhanced cardiac glutathione (GSH) levels, GSH/GSSG ratio and up-regulation of cardiac copper/zinc-superoxide dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activity and protein expression. Training also caused depletion of cardiac malondialdehyde (MDA) and protein carbonyls. Chronic L-NAME administration resulted in depletion of cardiac NO level, NOS activity, eNOS, nNOS and iNOS protein expression, GSH/GSSG ratio and down-regulation of cardiac CuZn-SOD, Mn-SOD, CAT, GSH-PX, glutathione-S-transferase (GST) activity and protein expression. Chronic L-NAME administration enhanced cardiac xanthine oxidase (XO) activity, MDA levels and protein carbonyls. These biochemical changes were accompanied by increases in BP and HR after L-NAME administration. Interaction of training and NOS inhibitor treatment resulted in normalization of BP, HR and up-regulation of cardiac antioxidant defense system. The data suggest that physical conditioning attenuated the oxidative injury caused by chronic NOS inhibition by up-regulating the cardiac antioxidant defense system and lowering the BP and HR in rats.
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PMID:Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. 1200 27

In previous works we demonstrated that 2-methyl-1,4-naphthoquinone (menadione) causes a marked increase in the force of contraction of guinea pig and rat isolated atria. This inotropic effect was significantly higher in the guinea pig than in the rat and was strictly related to the amount of superoxide anion (O(2)(*-)), generated as a consequence of cardiac menadione metabolism through mitochondrial NADH-ubiquinone oxidoreductase. The present study was designed to further elucidate the basis of these quantitatively different positive inotropic responses. To this purpose, we measured O(2)(*-) and hydrogen peroxide (H(2)O(2)) produced by mitochondria isolated from guinea pig and rat hearts in the presence of 20 microM menadione. Moreover, we evaluated the menadione detoxification activity (DT-diaphorase) and the antioxidant defences of guinea pig and rat hearts, namely their GSH/GSSG content, Cu/Zn- and Mn-dependent superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) activities. Our results indicate that DT-diaphorase activity and glutathione levels were similar in both animal species. By contrast, guinea pig mitochondria produced greater amounts of O(2)(*-) and H(2)O(2) than those of rat heart. This is probably due to both the higher Mn-SOD activity (2.93 +/- 0.02 vs. 1.95 +/- 0.06 units/mg protein; P < 0.05) and to the lower Gpx activity (10.09 +/- 0.30 vs. 32.67 +/- 1.02 units/mg protein; P < 0.001) of guinea pig mitochondria. A lower CAT activity was also observed in guinea pig mitochondria (2.40 +/- 0.80 vs. 6.13 +/- 0.20 units/mg protein; P < 0.01). Taken together, these data provide a rational explanation for the greater susceptibility of guinea pig heart to the toxic effect of menadione: because of the greater amount of O(2)(*-) generated by the quinone and the higher mitochondrial Mn-SOD activity, guinea pig heart is exposed to more elevated concentrations of H(2)O(2) that is less efficiently detoxified, because of lower Gpx and CAT levels of mitochondria.
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PMID:Role of antioxidant defences in the species-specific response of isolated atria to menadione. 1210 91

Type II fiber loss and reactive oxygen species (ROS)-induced damage are hallmarks of muscle aging. The aim of this study was to analyze whether there exists a relationship between age-dependent changes in cellular antioxidant capacity and type II fiber loss in aged human skeletal muscles. Forty-five male and female subjects ranging in age from 65 to 90 year-old were divided into +40 and -40% type II fiber groups. We measured both total and Mn superoxide dismutase (total and MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities. We also measured the reduced and oxidized forms of glutathione (GSH and GSSG) and lipid peroxide (LPO) levels. Total SOD activity was lower in the -40% type II fiber group than in the +40% group; MnSOD tended to be lower but data are not statistically consistent. Both GSHPx and CAT activities remained unchanged; as did GSH, GSSG and GSH/GSSG ratio. Finally, muscle samples with -40% type II fibers had a significantly higher LPO content compared to those with +40% type II fibers. In summary, a relationship between human skeletal muscle aging, type II fiber loss and ROS reactions seems to exist.
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PMID:Antioxidant pathways in human aged skeletal muscle: relationship with the distribution of type II fibers. 1221 57

HeLa cell line stably transfected with the tat gene from human immunodeficiency virus type 1 has a decreased antioxidant potential. In this work, we used this model to investigate the effect of a high glucose level (20 mM) on the glucose induced cytotoxicity and on the antioxidant system. In comparison to cell culture under control medium, HeLa-wild cell cultured under 20 mM glucose did not exhibit necrosis or apoptosis, contrary to HeLa-tat cell presenting a significant increase in necrotic or apoptotic state. Moreover after 48 h culture under high glucose level the HeLa-tat proliferation rate was not higher than the one of HeLa-wild cells. In HeLa-wild cell high glucose level resulted in an induction of glutathione reductase activity in opposition to HeLa-tat cells where no change was observed. High glucose level resulted in 20% increase in GSSG/GSH ratio in HeLa-wild cells and 38% increase in HeLa-tat cells. Moreover, high glucose level resulted in a dramatic cytosolic thiol decrease and an important lipid peroxidation in HeLa-tat cells. No significant change of these two parameters was observed in HeLa-wild cells. In both cell lines, high glucose resulted in an increase of total SOD activity, as a consequence of the increase in Cu,Zn-SOD activity. High glucose did not result in an increase of Mn-SOD activity in both cell lines. As a consequence of tat tranfection Mn-SOD activity was 50% lower in HeLa-tat cells in comparison to HeLa-wild cells. This work emphasizes the importance of the antioxidant system in the glucose induced cytotoxicity.
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PMID:Characterization of free radical defense system in high glucose cultured HeLa-tat cells: consequences for glucose-induced cytotoxicity. 1244 27

Reactive oxygen species (ROS) such as superoxide anion (O(2)(*-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radical (*OH) are produced constantly in aerobic organisms. Submandibular glands of rats treated with isoproterenol (ISO) were analysed in respect to the level of superoxide dismutase (SOD), lipoperoxidation, protein oxidation and glutathione (GSH)/GSSG. Although ISO response is very well studied in salivary glands cells, the effect of ISO treatment on ROS productions or on SOD activation is not known. SOD activity increased after isoproterenol subcutaneous injection. In contrast, cycloheximide, a protein synthesis inhibitor, was found to decrease the total SOD activity. The GSH/GSSG ratio and the lipoperoxidation were also found to be increased after isoproterenol injection, while the protein oxidation was not affected by the same treatment. Injection of isoproterenol after cycloheximide treatment resulted in the recovery of the total SOD activity. This increase of activity is related to the amount of MnSOD isoform as shown by Western blot analysis. Our results suggest that the antioxidant protection of SOD may be activated during the salivary glands ISO treatment and that the mitochondrial MnSOD has an important role in the oxidative stress process.
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PMID:Modulation of SOD activity in rat submandibular glands. 1264 32

Renin-angiotensin system (RAS) inhibition can attenuate the effects of aging on renal function and structure; however, its effect on mitochondrial aging is unknown. To investigate whether an angiotensin-converting enzyme inhibitor (enalapril) or an angiotensin II receptor blocker (losartan) could mitigate age-associated changes in kidney mitochondria, male Wistar rats (14 mo old) received during 8 mo water containing either enalapril (10 mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no additions (Old). Four-month-old untreated rats (Young) were also studied. In Old rats mitochondrial respiratory control, ADP/O, nitric oxide synthase activity, and uncoupling protein 2 levels were lower (46, 42, 27, and 76%, respectively), and Mn-SOD activity was higher (70%) than in Young, Enal, and Los rats. In Old rats mitochondrial hydrogen peroxide production was higher than in both Young (197%) and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was lower than in both Young (80%) and Enal (57%) or Los (68%) rats. In Old rats electron microscopy showed effacement of microvilli in tubular epithelial cells, ill-defined mitochondrial cristae, lower mitochondrial numbers, and enhanced number of osmiophilic bodies relative to Young, Enal, or Los rats. In conclusion, enalapril and losartan can protect against both age-related mitochondrial dysfunction and ultrastructural alterations, underscoring the role of RAS in the aging process. An association with oxidative stress modulation is suggested.
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PMID:Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. 1270 17

Many individuals with cardiovascular diseases undergo physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and changes in cardiac nitric oxide (NO) and antioxidants in rats. Fisher 344 rats were divided into four groups treated as: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks), and (4) training+nitroglycerin for 8 weeks. Respiratory exchange ratio (RER), BP, and heart rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24 h after last treatments, hearts isolated, and analyzed. Physical conditioning significantly increased RER, cardiac NO levels, and endothelial eNOS protein expression. Training significantly enhanced cardiac glutathione (GSH) levels, GSH/GSSG ratio, and the up-regulation of cardiac copper/zinc-superoxide dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activities, and protein expression. Training also caused depletion of cardiac malondialdehyde (MDA) and protein carbonyls with a significant increase in RER without any change in BP and HR. Chronic nitroglycerin administration significantly increased cardiac NO levels and eNOS protein expression. Nitroglycerin administration significantly enhanced cardiac Mn-SOD, CAT, and GST activities, and protein expression with decreased MDA levels and BP. Interaction of training and chronic nitroglycerin treatment increased cardiac NO levels with enhanced eNOS and iNOS protein expressions, GSH/GSSG ratio, and the up-regulation of antioxidant enzymes. This interaction normalized BP and HR and increased RER. The data suggest that the interaction of physical training and chronic nitroglycerin treatment resulted in the maintenance of BP and RER by up-regulating the antioxidants and NO levels and by reducing the oxidative stress in the rat heart.
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PMID:Interaction of physical training and chronic nitroglycerin treatment on blood pressure, nitric oxide, and oxidants/antioxidants in the rat heart. 1286 Apr 43

Many cardiac patients undergo exercise conditioning with or without medication. Therefore, we investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP), aortic nitric oxide (NO), oxidants and antioxidants in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) ET+nitroglycerin. BP was monitored with tail-cuff method. The animals were sacrificed 24 h after the last treatments and thoracic aorta was isolated and analyzed. Exercise training on treadmill for 8 weeks significantly increased respiratory exchange ratio (RER), aortic NO levels, and endothelial nitric oxide synthase (eNOS) protein expression. Training significantly enhanced aortic glutathione (GSH), reduced to oxidized glutathione (GSH/GSSG) ratio, copper/zinc-superoxide dismutase (CuZn-SOD), Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) glutathione disulfide reductase (GR) activities and protein expressions. Training significantly depleted aortic malondialdehyde (MDA) and protein carbonyls without change in BP. Nitroglycerin administration for 8 weeks significantly increased aortic NO levels and eNOS protein expression. Nitroglycerin significantly enhanced aortic Mn-SOD, CAT, GR and glutathione-S-transferase (GST) activities and protein expressions with decreased MDA levels, protein carbonyls and BP. Interaction of training and nitroglycerin treatment significantly increased aortic NO levels, eNOS protein expression, GSH/GSSG ratio, antioxidant enzymes and normalized BP. The data suggest that the interaction of training and nitroglycerin maintained BP by up-regulating the aortic NO and antioxidants and reducing the oxidative stress in rats.
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PMID:Interaction of regular exercise and chronic nitroglycerin treatment on blood pressure and rat aortic antioxidants. 1473 77

Carboplatin, a second-generation platinum-containing anti-cancer drug, is currently being used against human cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. We have shown a dose-dependent nephrotoxicity of carboplatin in a rat model. However, the time response of carboplatin-induced renal injury has not been explored. This study investigated the time response of carboplatin-induced nephrotoxicity in rat. Male Wistar rats (250-300 g) were divided into two groups of 30 animals each and treated as follows: (1) control (saline, intraperitoneally) and (2) carboplatin (256 mg kg(-1), intraperitoneally). The animals (n = 6) from each group were sacrificed 1-5 days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine, blood urea nitrogen (BUN), and blood urea levels were increased significantly in response to carboplatin in a time-dependent manner, indicating potential nephrotoxicity. Carboplatin time-dependently increased the renal platinum concentration, renal xanthine oxidase activity, increased membrane lipid peroxidation (MDA) concentration, while ratio of reduced-to-oxidized glutathione (GSH/GSSG) depleted significantly, indicating oxidative renal injury. Renal anti-oxidant enzymes, such as cytosolic copper/zinc-superoxide dismutase (CuZn-SOD) and mitochondrial manganese (Mn)-SOD, catalase (CAT), and glutathione peroxidase (GSH-Px) activities were decreased significantly due to carboplatin 3-5 days post-treatment. The protein expressions of renal CuZn-SOD and Mn-SOD significantly depleted 3-5 days after carboplatin administration, indicating decline in de novo synthesis of enzyme proteins. The data suggested that carboplatin caused time-dependent oxidative renal injury, as evidenced by renal anti-oxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine BUN, and blood urea levels in rats.
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PMID:Time response of carboplatin-induced nephrotoxicity in rats. 1522 73

Aluminum (Al)-induced pro-oxidant activity and the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in the hippocampi of rats following administration of Al and/or melatonin. Two groups of male rats were intraperitoneally injected with Al (as Al lactate) or melatonin only, at doses of 7 and 10 mg/kg/day, respectively, for 11 weeks. During this period, a third group of animals received Al (7 mg/kg/day) plus melatonin (10 mg/kg/day). At the end of the treatment, hippocampus was removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Gene expression of Cu-ZnSOD, MnSOD, GPx, and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu, and Zn concentrations in hippocampus were also determined. The results show that Al exposure promotes oxidative stress in the rat hippocampus, with an increase in Al concentrations. The biochemical changes observed in this tissue indicate that Al acts as pro-oxidant agent, while melatonin exerts antioxidant action by increasing the mRNA levels of the antioxidant enzymes evaluated. The protective effects of melatonin, together with its low toxicity and its capacity to increase mRNA levels of antioxidant enzymes, suggest that this hormone might be administered as a potential supplement in the treatment of neurological disorders in which oxidative stress is involved.
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PMID:Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration. 1558 78


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