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 have long been well known by physicists but have only interested biologists since 1969 when Fridovich showed that O2 was produced during an enzymatic oxidation. O2 and related radicals are highly toxic. This implies that, in all aerobic cells, mechanisms exist which inactivate free radicals as soon as they are produced by oxidative metabolism. O2 radicals are eliminated by a family of enzymes called superoxide dismutases (SOD). These SOD are present in the cytosol (CuSOD) and in the mitochondria (MnSOD). Overproduction of free radicals, originating in molecular oxygen, may explain the lesions which result from inflammation, ischemia, and radiation exposure. Free radicals can cause damage to membranes, macromolecules, and DNA. Whether free radical production is mainly intracellular or extracellular may determine to a degree which kind of damage will occur.
 ...
PMID:[Free radicals in medicine and biology]. 629 65

Brain injury in Mongolian gerbil (Merisones unguiculatus) was induced by occluding bilateral common carotid arteries for 60 min followed by reperfusion for 5 or 30 min. Oxygen free radicals in brain tissue were measured by electron spin resonance (ESR) technique, malondialdehyde (MDA) was measured by fluorescence spectrometry, and superoxide dismutase (SOD) was measured by nitrite kit. Oxygen free radicals and MDA were not significantly increased, but activities of T-SOD and Mn-SOD were decreased after 60 min of cerebral ischemia. The free radicals were increased at 5-min reperfusion, and then reduced to the level of ischemia group after 30-min reperfusion. MDA was increased remarkably after reperfusion of 30 min, whereas the activity of SOD continued to decrease. Sodium diethyldithiocarbamate (DTC), i.v. 5-100 mg.kg-1 15 min before occlusion, decreased the production of MDA and increased the activities of T-SOD and Mn-SOD. The formation of oxygen free radicals was depressed by i.v. DTC 50 mg.kg-1. The result suggested that the protective effects of DTC on ischemia-reperfusion-induced brain injury might be induced by scavenging the oxygen free radicals, increasing the Mn-SOD activity and decreasing the production of MDA.
 ...
PMID:[Effects of sodium diethyldithiocarbamate on ischemia-reperfusion-induced brain injury in Mongolian gerbil]. 771 79

Pretreatment of the gerbil brain with a 2-min period of sublethal ischemia protects against neuronal damage following a subsequent 3-min period of ischemia, which normally destroys pyramidal neurons in the CA1 region of the hippocampus. To clarify the role of superoxide dismutase (SOD) in this ischemic tolerance, we immunohistochemically investigated the alterations in copper-zinc SOD (CuZnSOD) and manganese SOD (Mn-SOD) in the gerbil hippocampus following 3-min ischemia with or without the first mild ischemia. Normal hippocampus showed an intense CuZnSOD immunostaining in pyramidal neurons but relatively less MnSOD immunostaining. MnSOD, but not CuZnSOD, immunoreactivity increased after the first ischemia. Both CuZnSOD and MnSOD immunoreactivities decreased throughout the hippocampus 4 h after 3 min of ischemia both with and without the first ischemia. The immunostaining recovered in resistant regions (CA3 and dentate gyrus) after 1 day in both groups and in the pretreated CA1 after 2 days. Without pretreatment, however, the immunostaining never recovered in the vulnerable CA1 region. The results suggest that ischemic tolerance is induced in part by enhanced synthesis of MnSOD in the tolerance-acquired hippocampus. Both CuZnSOD and MnSOD immunoreactivities decreased after the second ischemia even in the pretreated hippocampus in the early reperfusion periods, but ischemic tolerance facilitated the recovery from the postischemic reductions in SOD immunoreactivity.
 ...
PMID:Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance. 779 39

Decreased endogenous superoxide dismutase (SOD) activity has been implicated in free radical-mediated reperfusion injury of the ischemic myocardium. Antioxidant enzymes have been added to the modalities of reperfusion therapy of acute myocardial infarction based on this observation. We measured the content of MnSOD specific protein, activity of Mn and Cu, ZnSODs, and MnSOD mRNA in the working isolated rat heart subjected to various durations of ischemia and reperfusion. Recovery of mechanical function was monitored and lactate and lactic dehydrogenase released in the coronary effluent before and after ischemia were measured. In this model with reversible or irreversible myocardial injury, we noted no change in the myocardial MnSOD specific protein content and, contrary to some previous observations, no change in the activity levels of Mn or Cu,ZnSODs. Our results suggest that free radical-mediated damage in the heart during ischemia and reperfusion is probably not due to impaired activity or degradation of native SODs.
 ...
PMID:Lack of change in MnSOD during ischemia/reperfusion of isolated rat heart. 826 52

Reactive oxygen species such as superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxy radical (OH) possess potent oxygen toxicity to cells. Superoxide dismutases (SODs) are metalloenzymes that are essential for dismutation of O2- to H2O2 and O2. SODs are important initial components in the cellular defense against oxygen toxicity since O2- can react with H2O2 to generate single oxygen and hydroxy radicals, which are even more reactive and cytotoxic than O2- or H2O2. In mammalian tissues three superoxide dismutases (SODs) designated Cu,Zn-SOD, Mn-SOD and extracellular SOD exist. These enzymes play an important role in the antioxidant defense system against superoxide anion (O2-) generated in vivo and may be involved in various pathophysiological processes including inflammation, cancer diabetes, aging and ischemia. (1) The role of superoxide anion in ovulation and luteal function was investigated the localization of Cu, Zn-SOD and Mn-SOD in rat and human ovary by immunohistochemical methods. Cu,Zn-SOD was present in granulosa cells of mature Graafian follicles and growing follicles and Mn-SOD was present in luteal cells of the corpus luteum in rat. (2) To investigate the relationship between active oxygen radical-scavenge system and ovulatory mechanism in human. Mn-SOD was found in granulosa cells and theca cells of mature follicles, luteal cells of corpus luteum and epithelial cells of fallopian tubes. Cu,Zn-SOD was localized in theca cells of mature follicles, margin of corpus luteum and epithelial cells of tubal isthmus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Oxygen radicals-superoxide dismutase system and reproduction medicine]. 837 Oct 13

We examined antioxidant activity in the pre-conditioned canine myocardium with four 5-min episodes of regional ischemia and reperfusion. Immediately after repetitive brief ischemia, mitochondrial Mn-superoxide dismutase (SOD) activity in the ischemic myocardium significantly increased compared with that in the nonischemic myocardium (18.7 +/- 2.1 vs. 14.9 +/- 1.0 U/mg protein, P < 0.05). Although no difference was seen in the activity between these regions after 3 h of the sublethal ischemia, a significant increase in the activity of the ischemic myocardium reappeared after 24 h compared with that of the nonischemic myocardium (26.7 +/- 0.9 vs. 20.8 +/- 0.9 U/mg protein, P < 0.05). Mn-SOD content increased gradually in the ischemic myocardium after sublethal ischemia, with a peak after 24 h (2.8 +/- 0.1 vs. 2.1 +/- 0.1 microgram/mg protein, P < 0.05). There were no differences in the activity and content of Cu, Zn-SOD between these regions after sublethal ischemia. Activities of glutathione peroxidase and reductase were significantly higher and lower, respectively, in the ischemic myocardium than those of the nonischemic myocardium immediately after repetitive brief ischemia, but no differences between these regions were seen in activities after 3 or 24 h. These results indicate that a brief ischemic insult alters myocardial antioxidant activity not only immediately after but also 24 h after sublethal ischemia.
 ...
PMID:Sublethal ischemia alters myocardial antioxidant activity in canine heart. 843 Aug 58

We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection. In the isolated heart model, the rats were pretreated with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method. After 20 min of ischemia which was induced by a ligation of a coronary artery, reperfusion-induced arrhythmias were observed. There were no significant differences in the incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration of the ventricular arrhythmias and also delayed the onset of arrhythmias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size expressed as a percentage of the area at risk was significantly reduced in the IL-1 alpha pretreated hearts compared with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk of ischemia-reperfusion injury.
 ...
PMID:Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat. 857 26

The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p < 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p < 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.
 ...
PMID:Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion. 940 79

We have recently developed a porcine model with naturally occurring hypertrophic cardiomyopathy (HCM). Similar to humans, occluded intramural coronary artery and damaged mitochondria are frequently observed in these animals in which the disease is thought to be associated with the local ischemia of myocardium. In view of antioxidant functions involved in the ischemic injury, we measured the expression of endogenous antioxidant enzymes in the tissues with and without HCM. The results showed a significant increase of Cu,Zn-superoxide dismutase (SOD), but not Mn-SOD, and decrease of catalase (CAT) activities in the various areas of HCM hearts. It was demonstrated that SOD/CAT ratios in the HCM hearts were significantly higher than those in normals and were found to be dramatically correlated with the severity of cardiac hypertrophy. The altered SOD/CAT ratio was also consistent with increase in lipid damage. We hypothesize that the elevated SOD combined with an inadequate amount of H2O2 scavenging enzyme may lead HCM heart at oxidative stress risk. However, the pathogenic role of imbalanced antioxidant enzyme needs to be further explored.
 ...
PMID:Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy. 944 21

The objectives of this study were to (1) determine whether transgenic (Tg) mice overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) are protected from the deleterious effects of gut ischemia/reperfusion (I/R) and (2) compare the effectiveness of Tg SOD overexpression in attenuating I/R injury to intravascularly administered CuZn-SOD or manganese (Mn)-SOD. The accumulation of fluorescently labeled leukocytes and number of nonperfused sinusoids were monitored by intravital microscopy in livers of wild-type mice (C57BL/6), CuZn-SOD Tg mice, and wild-type mice receiving either CuZn-SOD or Mn-SOD. All parameters were measured for 1 hour after release of the occluded (for 15 minutes) superior mesenteric artery. Gut I/R in wild-type mice led to an increased number of stationary leukocytes, while reducing the number of perfused sinusoids (capillary no-reflow). All of these responses were significantly blunted in CuZn-SOD Tg mice, with a corresponding attenuation of liver enzyme release into plasma. Exogenously administered SOD had little or no effect on gut I/R-induced leukostasis or capillary no-reflow in the liver. These observations suggest a role for superoxide in gut I/R-induced leukostasis and hypoxic stress in the liver. Furthermore, the findings suggest that cellular localization of SOD activity is an important determinant of the protective actions of this enzyme in experimental models of I/R injury.
 ...
PMID:Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion. 975 38


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