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)

We investigated the effects of hypoxia/reoxygenation exposure on the barrier function of endothelial cell monolayers. Bovine pulmonary microvessel endothelial cells were grown to confluence on microporous filters (0.8-microns pore diameter) and exposed to hypoxia (0.1% O2 or PO2 approximately 1 mm Hg) for 2, 4, 12, or 24 hours, followed by reoxygenation with room air for a period ranging from 16 seconds to 2 hours. The transendothelial clearance rate of 125I-albumin was measured to determine the permeability of endothelial monolayers. Permeability increased twofold or fivefold over control values after 1 hour of reoxygenation in monolayers that had been exposed to either 12 or 24 hours of hypoxia. The response occurred within 5 minutes of reoxygenation, increased maximally by 40 minutes, and remained elevated with continuous reoxygenation for up to 2 hours. The increase in permeability was associated with F-actin reorganization, a change to spindlelike cells, and injured mitochondria. Immunoblot analysis indicated that neither hypoxia alone nor reoxygenation changed CuZn superoxide dismutase (SOD), MnSOD, and catalase levels. However, release of superoxide anions (O2-) into the extracellular medium increased by twofold within 40-60 minutes of reoxygenation. Treatment of endothelial cells with CuZnSOD (100 units/ml) for the 24-hour hypoxia period prevented O2- generation and approximately 50% of the increase in permeability. Higher CuZnSOD concentrations (greater than or equal to 200 units/ml) were not protective. Treatment with catalase (100-1,000 units/ml) inhibited the reoxygenation-induced increase in permeability at the highest catalase concentration (1,000 units/ml), suggesting a critical role of hydrogen peroxide in mediating the response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reoxygenation of endothelial cells increases permeability by oxidant-dependent mechanisms. 156 6

Increases in lipid peroxide in kidneys of rats treated with cisplatin were examined in relation to decreases in the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Mn-SOD, glutathione peroxidase (GSHpx), glutathione S-transferase (GST) and catalase. The activities of catalase, GSHpx and GST in the kidney and the liver were significantly decreased after cisplatin administration. The decrease of GST activity in the kidney was 87.3%, this was the largest decrease among these enzymes in the tissues examined. Cu,Zn-SOD activity significantly decreased only in the kidney. In contrast, the activities of these enzymes in the heart and the lung, which showed no increase in lipid peroxide in our previous study, were not significantly decreased. Cisplatin does not directly increase lipid peroxidation in vitro; therefore, the increase of lipid peroxide in the kidneys of these rats treated with cisplatin can be attributed to a decrease in the activities of lipid peroxide-protecting enzymes.
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PMID:Effect of cisplatin on the activities of enzymes which protect against lipid peroxidation. 157 81

Anaerobically grown Escherichia coli contain an enzymatically active iron superoxide dismutase (Fe2-FeSOD) and an inactive iron-substituted manganese superoxide dismutase (Fe2-MnSOD). The anaerobic electron sink, nitrate plus paraquat, enhanced biosynthesis of the MnSOD polypeptide, with accumulation of inactive Fe2-MnSOD. The oxidant, diamide, in contrast, allowed anaerobic production of the active forms of MnSOD, i.e. Mn2-MnSOD and Mn/Fe-MnSOD. Nutritional supplementation with Mn(II) favored occupancy of the MnSOD active site with manganese and allowed anaerobic accumulation of Mn2-MnSOD in the absence of diamide. Enrichment of the anaerobic growth medium with Fe(II) both suppressed biosynthesis of the MnSOD polypeptide and inhibited formation of the active manganese-containing forms. A tac-sodA operon fusion was used to examine the effects of chelating agents and metals on maturation of nascent MnSOD, independent from the transcriptional effects these agents impose. Isopropyl-1-thio-beta-D-galactopyranoside (IPTG) elicited anaerobic biosynthesis of MnSOD, which accumulated as the inactive Fe2-MnSOD. Diamide, with IPTG, allowed formation of active Mn/Fe-MnSOD while 1,10-phenanthroline with IPTG resulted in accumulation of Mn2-MnSOD. These results suggest that iron participates in the redox-sensitive control of the formation of active MnSOD at two levels, i.e. that of transcription as well as that of maturation. During maturation of the nascent MnSOD polypeptide, iron and manganese compete for the metal-binding site; anaerobic conditions favor iron-binding, whereas oxidants, such as dioxygen or diamide, favor binding of manganese.
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PMID:Transcriptional and maturational effects of manganese and iron on the biosynthesis of manganese-superoxide dismutase in Escherichia coli. 157 50

Human retinal pigment epithelium (RPE) contains two genetically distinct forms of superoxide dismutase (SOD) enzymes that scavenge harmful superoxide anions. Biochemical and immunochemical techniques were used to compare levels of copper-zinc- and manganese-containing forms of SOD (CuZn-SOD and Mn-SOD) in human adult and fetal RPE cells. It was found that Mn-SOD activity was higher in adult than fetal RPE cells, both in vivo and in vitro. Immunolocalization of Mn-SOD in cultured RPE cells showed a greater reactivity in the mitochondria of the adult cells. Primary cultures of adult RPE contained cells with various patterns of mitochondria as shown by immunolabeling for Mn-SOD. Adult RPE cells were more resistant to the effects of a superoxide generator, paraquat, which appeared to disrupt mitochondrial integrity as judged by staining with rhodamine 123. These results suggest that high levels of Mn-SOD protect mitochondria from oxidative damage that probably occurs with aging in the RPE.
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PMID:Mitochondrial superoxide dismutase in mature and developing human retinal pigment epithelium. 158 97

In a previous study we have shown that chronic administration of (-)deprenyl increases activities of superoxide dismutase (SOD) and catalase (CAT) in rat striatum (1). The present study attempted to clarify how specific the effect of deprenyl is to certain tissues and brain regions in the rat. Two mg/kg/day of deprenyl was continuously infused s.c. in young male Fischer-344 rats. On the 22nd day, rats were sacrificed and enzyme activities of SOD and CAT were determined in several different brain regions and the liver. Activities of both SOD and CAT were significantly increased in striatum and substantia nigra but not in hippocampus, cerebellum or liver. Both types of SOD (i.e. Cu Zn-SOD and Mn-SOD) were significantly increased in striatum, substantia nigra. Interestingly, in cerebral cortices of three different regions, activities also tended to increase (especially those of Mn-SOD), although the increase was not so striking as in substantia nigra and striatum. The results confirm the previous observation that (-)deprenyl can increase free radical scavenger enzyme activities in striatum and provide further evidence that this effect is selective to certain brain regions and tissue types.
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PMID:The ability of (-)deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective. 159 26

In the present study, we have assayed the enzymatic activity of Cu,Zn-SOD, Mn-SOD, GSH-Px, GSH-Red, Cat, and G6PD in rat retina as a function of age. Conjugated diene levels and MDA formation were also determined. The conjugated diene levels in rat retina were found to increase significantly with age, accompanied by a marked decrease in GSH-Px and Cat activities. No age-related change in MDA levels and in GSH-Red and G6PD activity was found, whereas a significant increase in SOD activity was observed between 1 and 4 months. Decreased GSH-Px and Cat activity is related to increased lipid peroxidation with age.
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PMID:Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. 160 66

To investigate the role of superoxide dismutase (SOD) in the ovulatory process, SOD isozymes and their mRNAs were determined in the ovary of 22-day-old rats. After treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), ovarian activity of Mn-SOD decreased markedly while Cu/Zn-SOD remained unchanged. However, the ovarian level of mRNA for Mn-SOD markedly increased after hCG-treatment while that for Cu/Zn-SOD decreased only slightly. Ovulation was inhibited by intravenous injection of a long-acting SOD. These results suggested that superoxide radicals in the ovary might play a critical role in the mechanism for hCG-induced ovulation.
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PMID:Dynamic aspects of ovarian superoxide dismutase isozymes during the ovulatory process in the rat. 160 8

1. The activity of antioxidant defense enzymes (SOD, CAT, GSH-Px and GST) was analysed during the autumn and winter in the ground squirrel adapted to 30 degrees C and subsequently exposed to cold for 6 and 24 hr. 2. The liver CAT activity as well as the IBAT CAT and GSH-Px activities differed between animals adapted to 30 degrees C, studied in autumn, and those studied in winter. 3. MnSOD activity in the liver was increased in autumn but decreased in winter after 6 hr cold exposure reaching the control level 24 hr later. Cold exposure induced a decrease in CAT activity (except after 24 hr cold exposure in winter) and an increase in GSH-Px activity. Lower GST activity was found after 24 hr exposure to cold in winter. 4. The IBAT SOD activity decreased under the influence of cold during both seasons with a tendency to return to the control level only in winter. Cold exposure produced a decrease in GST in both seasons and CAT activity in autumn. GSH-Px activity was increased in winter only. 5. The results indicate a seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel. Seasonal influence was evidenced in animals exposed to cold as well.
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PMID:Seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel (Citellus citellus): the effect of cold. 161 72

HA-1 hamster fibroblasts receiving fresh media every 24 h were continuously passaged in progressively increasing O2 concentrations for 18 mo (designated O2R95). These cells were significantly more resistant than parental HA-1 to clonogenic inactivation mediated by 95% O2 without media replacement. The O2R95 cell line exhibited increases in the activities of catalase (CAT), Mn superoxide dismutase (MnSOD), Cu,Zn superoxide dismutase (Cu,Zn SOD), and glutathione peroxidase (GPx). O2R95 cells demonstrated uniformly distributed increased staining for CAT, MnSOD, Cu,Zn SOD, and GPx proteins, as determined by immunohistochemistry. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a toxic byproduct of lipid peroxidation implicated in mechanisms of O2 toxicity, was examined in HA-1 and O2R95 cell lines. O2R95 cells were significantly more resistant to 4HNE cytotoxicity, which was accompanied by a significant increase in 4HNE metabolism. O2R95 cells also demonstrated an increase in total glutathione (GSH) and glutathione S-transferase (GST) activity, an enzymatic system believed to be involved with 4HNE metabolism. Furthermore, homogenates from O2R95 cells consumed greater quantities of 4HNE in the presence of NADPH (but not NADH, NAD+, or NADP+), suggesting that an enzyme(s) utilizing NADPH contributes to 4HNE metabolism, resistance to 95% O2 and 4HNE as well as increased total GSH, antioxidant enzyme activities, and NADPH-dependent metabolism of 4HNE, persisted in O2R95 cells for 75 days of growth in 21% O2. These findings are compatible with the hypothesis that aldehydic byproducts of lipid peroxidation contribute to mechanisms of O2 toxicity and the selective pressure exerted by exposure of cells to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable O2-resistant cell line: role of lipid peroxidation byproducts in O2-mediated injury. 161 58

Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1), and interleukin-6 (IL-6) are multifunctional cytokines produced by a number of cells in response to endotoxin. We have previously demonstrated (M.-F. Tsan, J. E. White, T. A. Santana, and C. Y. Lee. J. Appl. Physiol. 68: 1211-1219, 1990, and M.-F. Tsan, C. Y. Lee, and J. E. White. J. Appl. Physiol. 71: 688-697, 1991) that tracheal insufflation of 5 micrograms of TNF-alpha or 1 microgram of IL-1 markedly protects rats against O2 toxicity and enhances pulmonary Mn superoxide dismutase (Mn SOD) activity. We now report that TNF-alpha and IL-1 at subprotective doses, e.g., 1 and 0.2 micrograms, respectively, act synergistically in protecting rats against O2 toxicity. Likewise, TNF-alpha and IL-1 at 0.005 microgram/ml each act synergistically in enhancing endothelial cell Mn SOD, but not Cu,Zn SOD mRNA levels. IL-6 at 5 or 10 micrograms provides no protective effect in rats against O2 toxicity and at up to 0.5 microgram/ml has no apparent effect on endothelial cell Mn or Cu,Zn SOD mRNA levels. However, IL-6 markedly enhances TNF-alpha- and IL-1-induced increases in Mn SOD mRNA levels and O2 tolerance. These results support an important role of Mn SOD in the protection against O2 toxicity.
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PMID:IL-6 enhances TNF-alpha- and IL-1-induced increase of Mn superoxide dismutase mRNA and O2 tolerance. 163 26


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