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)

Pancreatic carcinoma is one of the most devastating neoplasms with regard to its resistance to conventional therapy. In a previous report, we found that endogenous tumor necrosis factor (enTNF) exerts an intracellular protective effect against exogenous TNF- and Adriamycin (ADM)-induced cytotoxicity by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD). We also know that glutathione S-transferase pi (GST-pi) and glutathione (GSH) also scavenge OFR. It remains unclear to what extent enTNF and MnSOD induced by enTNF regulate the sensitivity to ADM and exogenous TNF among different carcinoma cells. In this study, we examined the relationship between ADM and exogenous TNF sensitivity and en-TNF expression and MnSOD activity in four pancreatic carcinoma lines. We determined whether ADM and exogenous TNF sensitivity could be predicted by measuring enTNF expression and MnSOD activity in the carcinoma cells. The sensitivity to TNF and ADM varied with the cell lines, and TNF sensitivity correlated well with Adriamycin sensitivity. Moreover, enTNF expression and Mn-SOD activity correlated positively with resistance to ADM and exogenous TNF. When MIAPaCa-2 cells, which had the lowest enTNF expression and the highest sensitivity to exogenous TNF and ADM, were transfected with the nonsecretory-type human TNF gene (pTNF delta pro) to increase enTNF synthesis, their intracellular MnSOD activity and exogenous TNF and ADM resistance were increased. These findings suggest that MnSOD plays a critical role in scavenging OFR induced by ADM and exogenous TNF. enTNF is the most important factor that regulates the production of MnSOD. Therefore, it is plausible that inhibition of enTNF expression or MnSOD activity in pancreatic carcinoma would improve the efficacy of therapies for pancreatic carcinoma.
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PMID:Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells. 889

An increase in antioxidant enzyme activity after acute exercise and exercise training have been reported by many investigators including our laboratory. This study was undertaken in order to determine whether an increase in activity of superoxide dismutase (MnSOD and CuZnSOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during exercise training was associated with the increased levels of respective mRNAs. Male Fisher-344 rats (age 77 weeks) were given exercise training for 9 weeks on the treadmill. Enzyme activity and mRNA's were measured in the heart tissue 23 hr after stopping exercise training. The heart tissues of exercised and sedentary control rats were used to isolate mRNAs encoding MnSOD, CuZnSOD, CAT and GSH-Px by northern blotting experiments. The intensities of mRNA bands were measured by densitometric scanning of the autoradiograms. Northern blot for tubulin was used to normalize the respective intensities. Compared to sedentary controls, the level of mRNAs of enzymes MnSOD, CAT and GSH-Px were found to increase by 126 +/- 5, 133 +/- 6, and 138 +/- 5 percent of sedentary control (mean +/- SEM) respectively, due to exercise training. Corresponding values for these enzyme activity were 153 +/- 19%, 255 +/- 7%, 133 +/- 2% of sedentary control. These results suggest that post-translational modification of these enzyme activity increased in response to exercise training more than increased transcription in aged rats.
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PMID:Comparative effects of exercise training on transcription of antioxidant enzyme and the activity in old rat heart. 895 Jan 34

The purpose of this study was to determine the antioxidant enzyme activities in renal tissues of early stage ddY mice, an animal model for primary IgA nephropathy. Eight- and 40-week-old ddY female mice and normal healthy Balb/c female mice were used in this study. The levels of Cu/Zn-SOD, Mn-SOD, and GSH-PX activities in the renal cortex were significantly higher in 40-week-old ddY mice than in Balb/c control mice of the same age; no change of catalase activity was observed. There were no significant differences in the levels of Cu/Zn-SOD, Mn-SOD, GSH-PX, and catalase activities between the ddY mice and Balb/c mice at 8 weeks of age. Urinary protein was slightly higher in 40-week-old ddY mice. IgA or C3 was deposited at low levels in the glomerular mesangial areas of 8-week-old ddY mice. Marked depositions of IgA and C3 extended from the glomerular mesangial areas to the capillary walls of 40-week-old ddY mice. Expansion of glomerular mesangial matrices and mild mesangial cell proliferation was observed in 40-week-old ddY mice. Antioxidant enzyme activities in the renal cortex were already increased in the early stage IgA nephropathy in 40-week-old ddY mice. These findings suggest that measurements of antioxidant enzyme activities in the renal cortex of 40-week-old ddY mice was useful for evaluation of the pathogenesis of renal involvement in the early stage of IgA nephropathy.
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PMID:Detection of antioxidant enzyme activities in renal tissues of early stage IgA nephropathy in ddY mice. 895 8

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)] in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.
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PMID:Antioxidant defense system in diabetic kidney: a time course study. 904 69

The activities of superoxide dismutases (total, cytoplasmic and mitochondrial) and glutathione peroxidase were measured in 10 cancerous and 10 non-cancerous adjacent human kidney tissues. Total (T-SOD) and cytoplasmic (Cu, Zn-SOD) superoxide dismutase and glutathione peroxidase (GSH-Px) activities were found lower in cancerous tissues compared with those of non-cancerous ones. However, no difference was found between the mitochondrial (Mn-SOD) superoxide dismutase activities of the tissues. Similarly, no differences were observed between the enzyme activity values of the tissues at stage I-II and III-IV renal cancer. In correlation analysis the positive relation found between Cu, Zn-SOD and GSH-Px enzymes in the non-cancerous tissues was found to be absent in the cancerous ones. The results suggest that enzymatic free radical defense mechanism is significantly reduced in the cancerous human kidney tissues due to depressed Cu, Zn-SOD and GSH-Px activities.
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PMID:Activities of superoxide dismutase and glutathione peroxidase enzymes in cancerous and non-cancerous human kidney tissues. 920 31

Previous studies in conscious pigs have demonstrated that a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles renders the heart relatively resistant to myocardial stunning 24 h later [late preconditioning (PC) against stunning] by an unknown mechanism. Since oxygen radicals contribute importantly to myocardial stunning and since antioxidant enzymes have been reported to be upregulated 24 h after PC in dogs and rabbits, we tested the hypothesis that late PC against stunning is related to an increase in endogenous antioxidant defenses. Chronically instrumented conscious pigs underwent a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles (preconditioned group, n = 11) or received no intervention (control group, n = 5). Twenty-four hours later, pigs were killed and the myocardial levels of Mn superoxide dismutase (SOD), Cu-Zn SOD, catalase, glutathione (GSH) peroxidase, GSH reductase, GSH, GSH disulfide, alpha-tocopherol, and ascorbate were measured. There were no differences in any of the enzymatic or nonenzymatic antioxidants between the ischemic and nonischemic regions in the preconditioned group or between the control and the preconditioned group. Thus, when a marked protection against stunning was present (24 h after PC), no alteration in antioxidant defenses was observed. These results indicate that, in conscious pigs, late PC against myocardial stunning is not mediated by increased endogenous antioxidant defenses, thereby refuting one of the major current hypotheses regarding this phenomenon.
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PMID:Late preconditioning against stunning is not mediated by increased antioxidant defenses in conscious pigs. 936 27

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.
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PMID:Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion. 940 79

Liver antioxidant enzyme activities, mRNA abundance, and glutathione (GSH) status were investigated in male Sprague-Dawley rats placed in an enclosure module aboard Space Shuttle STS-63 for 8 d (F, n = 6). F animals were compared to rats housed in an enclosure module on the ground (G, n = 9), which simulated the vibration and temperature conditions associated with launch and flight, and rats kept under conventional ground vivarium conditions in individual cages (V, n = 6). Spaceflight significantly decreased catalase, GSH reductase, and GSH sulfur-transferase activities in the liver (p < .05). Neither enzyme activity nor enzyme protein content of Cu-Zn and Mn superoxide dismutase (SOD) was affected by flight. The relative abundance of mRNA for Cu-Zn SOD and catalase was significantly decreased comparing F with G rats (p < .05). Spaceflight resulted in a dramatic decrease of liver GSH, glutathione disulfide, and total GSH contents (p < .01), which were accompanied by a lower gamma-glutamyl transpeptidase activity (p < .05). F rats showed a 47% (p < .05) increase in liver malondialdehyde concentration compared to G and V rats. Liver protein content was not affected by flight. These results indicate that spaceflight can downregulate antioxidant defense capacity and elicit an oxidative stress in the liver.
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PMID:Spaceflight downregulates antioxidant defense systems in rat liver. 943 15

In order to investigate the radioresistance mechanism of human carcinoma cells, we measured intracellular manganese- (Mn-) and copper/zinc- (Cu/Zn-) superoxide dismutases (SODs), glutathione (GSH) and poly (ADP-ribose) polymerase (PARP) in radioresistant N10 and its parental KB cell lines. The Mn-SOD level was 1.3-fold less in N10 than in KB, but Mn-SOD was induced at 1.3 to 1.5-fold higher level in N10 than in KB by X-irradiation (4 Gy). Cu/Zn-SOD in N10 showed a higher level than that in KB both without and with irradiation. In addition, N10 had a 1.65-fold higher GSH level than did KB and became radiosensitive on treatment with buthionine sulfoximine, an inhibitor of GSH. Furthermore, PARP mRNA was highly expressed in N10 as compared to KB under unirradiated conditions. X-Irradiation reduced the PARP mRNA level in KB in a time-dependent manner, whereas the PARP mRNA level in N10 was still high at 6 h postirradiation. Assay for PARP activity demonstrated an approximately 3-fold higher activity in N10 than in KB under unirradiated conditions. X-Irradiation caused a rapid induction of PARP activity within 1 h in both cell lines, but treatment of cells with nicotinamide, a PARP inhibitor, markedly reduced the enzyme induction in N10, but not in KB, and potentiated the radiosensitivity in N10. These factors may all contribute to the radioresistance of the N10 cell line.
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PMID:Levels of superoxide dismutases, glutathione, and poly(ADP-ribose) polymerase in radioresistant human KB carcinoma cell line. 943 82

Both clinical and experimental evidence indicates that AIDS-related Kaposi's sarcoma (AIDS-KS) has a multifactorial pathogenesis with factors such as HIV viral load, latent virus induction, and opportunistic infections contributing to disease progression. However, a consistent feature that unites these apparently diverse putative etiologic agents is sustained serum elevations of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). While virtually every cell responds to TNF-alpha with gene activation, the extent of TNF-alpha-mediated cellular signaling is regulated by a delicate balance between signal activation and signal arresting events. Reactive oxygen intermediates (ROI), which are generated as a consequence of TNF-alpha membrane interaction, are part of this TNF-alpha-initiated cellular activation cascade. Previous studies in our laboratory have shown that AIDS-KS cells possess impaired oxygen intermediate scavenging capacities, thereby establishing conditions permissive for the intracellular retention of ROI. In this study, we used cellular capacity to upregulate the cytoprotective enzyme superoxide dismutase (SOD) to address the extent of cellular response to TNF-alpha. Concurrent with the SOD analyses, nucleotide profiles were obtained to assess cellular bioenergetic responses during TNF-alpha challenge. Proliferative growth levels of mitochondrial (Mn)SOD activities showed an activity spectrum ranging from lowest activity in AIDS-KS cells, to intermediate levels in matched, nonlesional cells from the AIDS-KS donors, to highest activities in HIV normal fibroblasts. In contrast, following TNF-alpha challenge, the AIDS-KS and KS donor nonlesional cells showed a 11.89- and 5.86-fold respective increase in MnSOD activity, while the normal fibroblasts demonstrated a 1.35-fold decrease. Subsequent thiol redox modulation studies showed that only the normal fibroblast cultures showed a potentiation of TNF-alpha-mediated MnSOD upregulation following GSH depletion. In addition, provision of the GSH precursor, N-acetylcysteine during TNF-alpha challenge only diminished MnSOD activity and mitochondrial compartmentalization in the AIDS-KS cells, a finding that likely reflects the lower levels of reduced thiols in this cellular population. Our data, which show that a perturbation in their cellular thiol redox status accentuates AIDS-KS cellular responsiveness to TNF-alpha, suggest a biochemical rationale for the recognized TNF-alpha AIDS-KS clinical correlation.
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PMID:Thiol redox modulation of tumor necrosis factor-alpha responsiveness in cultured AIDS-related Kaposi's sarcoma cells. 951 60


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