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)

The pathogenesis of diabetic corneal epitheliopathy, one of the ocular complications frequently seen in diabetes patients, still remains to be elucidated. Hyperglycemia causes glycation of various proteins leading to the formation of superoxide radicals (O2.-). Copper, zinc-superoxide dismutase (Cu, Zn-SOD), a scavenger of superoxide radicals, whose function is complementary to manganese-SOD (Mn-SOD), is inactivated during glycation. As a first step to clarify whether depressed antioxidant activity is associated with diabetic corneal epitheliopathy or not, we investigated the expression of Mn-SOD mRNA (messenger ribonuclic acid) in streptozotocin-induced diabetic rat cornea by in situ hybridization using a digoxigenin-labeled Mn-SOD cDNA probe. Mn-SOD mRNA was detected in epithelial cell layer and endothelial cell layer of both diabetic rat cornea and normal rat cornea. However, the expression of Mn-SOD mMRA in the epithelial cell layer of diabetic rat cornea was weaker than that of normal rat cornea. These results suggest that decreased Mn-SOD activity might be one of factors causing diabetic corneal epitheliopathy.
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PMID:[Expression of Mn-SOD mRNA in streptozotocin-induced diabetic rat cornea by in situ hybridization]. 881 Feb 35

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.
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PMID:Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages. 884 37

We have studied the long-term effects of nicotinamide (NIC) on the synthesis of NO by insulin producing cells. NIC delays the formation of nitrite by interleukin (IL)-1 beta-(IL-1, 25 U/ml)-stimulated RINm5F cells, and previous exposure of cells to IL-1 for 15 h prevents this effect. The delay is associated with a lack of cytokine-induced inducible nitric oxide synthase (iNOS) enzyme activity in cell extracts. NIC (20 mM) inhibits NO synthase (NOS) activity in extracts from cells incubated with IL-1 for 6 h and 24 h, and oxyhemoglobin counteracts this inhibition. Hence, NIC could scavenge O2- and allow NO to inhibit the enzyme. The NO donor SIN-1 inhibits in a concentration-dependent manner iNOS activity, and the effect is potentiated by NIC. In intact cells, protection from NIC is associated with IL-1-induced expression of MnSOD activity, and reversible blockade of iNOS expression with pyrrolidine dithiocarbamate counteracts the NIC effect. We conclude that O2- plays a role in preventing NO inhibition of iNOS. The loss of this action coincides with the induction of MnSOD enzyme activity. In addition, the stimulation by NIC of IL-1-induced nitrite production in pyrrolidine dithiocarbamate-treated cells is a novel action that should be considered when the drug is proposed as potential agent for the prevention of insulin-dependent diabetes mellitus.
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PMID:Protection from nicotinamide inhibition of interleukin-1 beta-induced RIN cell nitric oxide formation is associated with induction of MnSOD enzyme activity. 889 50

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

Free radical-mediated damage to vascular cells may be involved in the pathogenesis of diabetic vasculopathy. The aim of this study was to compare the extent of glucose-induced oxidative stress in both vascular smooth muscle cells (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5 or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD, MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern analysis. Glutathione (GSH) was also measured. There was a significant increase in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/- 0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/- 0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n = 8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001). None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l glucose in either cell type. Both MnSOD activities and GSH concentrations were higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P < 0.05 and P < 0.02, respectively). These results demonstrate glucose-induced reduction of GSH in both cells, but only in VSMC is there evidence of oxidant damage in the form of lipid peroxidation, implying significant differences in intracellular responses to glucose between contractile cells in the macro- and microvasculature.
Diabetes 1998 May
PMID:Glucose-induced oxidative stress in vascular contractile cells: comparison of aortic smooth muscle cells and retinal pericytes. 958 53

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes. 2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes. 3. Male 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 consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals. 4. There was a significant (P < 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu-Zn-SOD activity increased (P < 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P < 0.05) in liver and pancreas. 5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern. 6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.
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PMID:Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. 985 60

Because programmed cell death (PCD) is an important mode of pericyte dropout in human diabetic retinopathy, whether increased oxidative stress in cells with diminished antioxidant defenses plays a causative role in the PCD process in diabetic pericytes has been studied. Ten diabetic and eight non-diabetic eye-bank eyes from 5 diabetic and 4 non-diabetic patients were included in this study. From individual neural retinas pericytes were isolated by a newly developed immunomagnetic technique. Total mRNA of the purified pericytes was isolated for quantitative reverse transcriptase (RT)-PCR assay. mRNA levels of a death protease (CPP32), the major enzyme that initiates the proteolytic cascade leading to cell death, were determined in association with the expression of antioxidative enzymes including glutathione peroxidase (GSH-Px), glutathione reductase, CuZn superoxide dismutase (SOD), MnSOD and catalase genes in pericytes. In comparison with pericytes from non-diabetic retinas, pericytes from diabetic retinas highly expressed CPP32 genes (4 +/- 0.6 fold increase, p < 0.01, n = 9). In diabetic pericytes, up-regulation of glutathione peroxidase (GSH-Px) (8.2 +/- 0.9 fold increase, p < 0.01, n = 9) and down-regulation of glutathione reductase (Gr) (4.1 +/- 0.4 fold decrease, p < 0.05, n = 9) and CuZnSOD (2.1 +/- 0.7 fold decrease, p < 0.05, n = 9) were observed. mRNA levels of MnSOD and catalase of diabetic pericytes did not differ significantly from those of non-diabetic pericytes. Overexpression of a member of interleukin-1 beta-converting enzyme (ICE) family, CPP32, indicated that the pericytes from diabetic retinas are in a "pre-PCD" state. This is the first evidence that the ICE family of death proteases is involved in pericyte dropout in diabetes. In these pre-PCD cells, the expression of antioxidant enzyme genes also was changed. Up-regulation of GSH-Px indicates a compensation mechanism to meet the demand of excessive glutathione in reduced form. Decreased levels of both glutathione reductase and CuZnSOD, despite the oxidative stress in the diabetic condition, suggest the breakdown of the antioxidant defense in pericytes. Most importantly, the altered gene profile of scavenging enzymes under diabetic conditions, correlating with overexpression of the cell death protease gene, together suggest increased oxidative stress as an etiological agent of pericyte dropout in diabetic retinopathy.
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PMID:Altered mRNA levels of antioxidant enzymes in pre-apoptotic pericytes from human diabetic retinas. 1009 40

In an attempt to discover the changes of superoxide dismutase (SOD) in the brain of diabetic state, we investigated the level of SOD in streptozotocin-induced diabetic rats (STZ-diabetic rats) using enzyme activity assay, Northern blotting analysis of mRNA levels and Western blotting of enzyme amount. Five discrete brain regions, cerebrocortex, hypothalamus, hippocampus, the remaining non-cortex cerebrum (NCC area) and cerebellum, were examined in STZ-diabetic rats to compare with age-matched normal rats. Higher levels of Mn-SOD including the activity, mRNA expression and immunoblot of enzyme were found in all areas of the brain from STZ-diabetic rats as compared with that in Wistar rats. Except in the cerebellum, similar changes of Cu,Zn-SOD were found in the brain of STZ-diabetic rats. These results indicate an increase of SOD both gene expression and activity in the brain of STZ-diabetic rats. This alteration of SOD may be one of the important factors for the vulnerability of the brain to oxygen free radicals or may be related to the pathophysiology of diabetes.
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PMID:Changes of superoxide dismutase gene expression and activity in the brain of streptozotocin-induced diabetic rats. 1055 76

Previous studies have suggested that reactive oxygen species (ROS) are mediators in the teratogenic process of diabetic pregnancy. In an animal model for diabetic pregnancy, offspring of the H rat strain show minor dysmorphogenesis when the mother is diabetic, whereas the offspring of diabetic rats of a sister strain, U, display major morphologic malformations. Earlier studies have shown that embryonic catalase activity is higher in the H than in the U strain, and maternal diabetes increases this difference in activity. The aim of this study was to characterize the influence of genetic predisposition on diabetic embryopathy by comparing the mRNA levels of ROS-metabolizing enzymes in the two strains. We determined the mRNA levels of catalase, glutathione peroxidase, gamma-glutamylcystein-synthetase, glutathione reductase, and superoxide dismutase (CuZn-SOD and Mn-SOD) in day 11 embryos of normal and diabetic H and U rats using semiquantitative reverse transcription-polymerase chain reaction. The mRNA levels of catalase and Mn-SOD were increased in H embryos as a response to maternal diabetes, and no differences were found for the other genes. Sequence analysis of the catalase promoter indicated that the difference in mRNA levels may result from different regulation of transcription. Sequence analysis of the catalase cDNA revealed no differences between the two strains in the translated region, suggesting that the previously observed difference in the electrophoretic mobility in zymograms is due to posttranslational modifications. An impaired expression of scavenging enzymes in response to ROS excess can thus be an integral part of a genetic predisposition to embryonic dysmorphogenesis.
Diabetes 2000 Jan
PMID:Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain. 1061 56

To investigate whether the two free-radical scavengers, Cu, Zn- and Mn-superoxide dismutase (SOD), are changed in leukocytes of diabetic patients, and the alteration of these enzymes correlates with the diabetic state, we measured the activity and concentration of these enzymes in leukocytes from diabetic patients. Both Cu, Zn-SOD and Mn-SOD activities in neutrophils and lymphocytes were significantly lower in patients with non-insulin-dependent diabetes mellitus than in healthy controls. The concentrations of these enzymes in leukocytes from diabetic patients, however, did not differ from those in controls. Cu, Zn-SOD and Mn-SOD activities in neutrophils inversely correlated with HbA(1c) concentrations. Myeloperoxidase activity in leukocytes was significantly reduced in NIDDM patients. These findings suggest that changes in these enzymes may affect the susceptibility to infection and immunocompetence of patients with diabetes.
J Diabetes Complications
PMID:Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus. 1076


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