Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, it is well established that moderate calorie restriction or reduction in overall high calorie food intake prevents or forestalls the development of age-associated disease incidence such as breast cancer and renal disease in rodents. A similar approach could also readily be applied in humans for preventing the risk and rise of life-shortening diseases. Many age-associated diseases, particularly autoimmune diseases with viral etiology, appear to be exacerbated in the presence of adverse lipid intake such as an increased level of vegetable oils or trans-fatty acids from the usage of hydrogenated dietary oils. At present, nearly 35-40% of the total calories are from dietary fats and/or of lipid origin. Although usage of saturated fat, which increases cardiovascular disease, has been reduced to a large extent in the United States, consumption of both monounsaturated and polyunsaturated fats of omega-6 origin has either increased or simply been substituted in place of saturated fats. Further, for the past 50 years, a significant reduction in highly polyunsaturated fat consumption such as marine oil has also occurred specifically in the United States. The reduction in omega-3 lipids of marine or vegetable source occurs primarily because of short shelf life due to rancidity. However, the increased consumption of omega-6 or a vegetable source of oils and decreased omega-3 intake may increase in vivo the production of free radicals and higher proinflammatory cytokines. Our ongoing studies reveal that proinflammatory vegetable oil could increase autoimmune disease by increasing the free radical formation by decreasing the antioxidant enzyme mRNA levels, thereby further decreasing immune function, particularly the production of anti-inflammatory cytokines such as IL-2 and TGF beta mRNA levels. In contrast, omega-3 lipid intake in the presence of an antioxidant supplement appears to exert protection against autoimmunity by enhancing antioxidant enzymes and TGF beta mRNA levels and by preventing the rise in oncogene expression. However, detailed studies are required to establish the protective and deleterious role of different commonly consumed lipids or dietary oils by the general population, particularly during middle and aging years. Further, we also propose that combining nonsteroidal drug therapy along with moderate calorie reduction in the presence of more protective omega-3 dietary lipids of either marine or vegetable source and decreasing the levels of mono- and polyunsaturated lipids may provide additional protection against the age-associated rise in malignancy and autoimmune disorders.
 ...
PMID:Dietary lipids and risk of autoimmune disease. 805 Jan 92

The response of the glomerular mesangial cell to reactive oxygen species (ROS) has been implicated in the pathogenesis of several forms of inflammatory renal disease. As a model of glomerular inflammation, we studied the effects of heat-aggregated immunoglobulin G (HAG), an experimental immune complex, and interleukin-1 (IL-1) on the expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), in primary cultures of rat mesangial cells. Following exposure to either HAG or IL-1 beta, increased steady-state MnSOD mRNA levels were observed and an additive effect was seen following co-treatment with HAG and IL-1 beta. No change was observed in steady-state levels of copper/zinc superoxide dismutase mRNA with HAG or IL-1 beta exposure. RNA protein synthesis inhibitor experiments demonstrated that the HAG- and IL-1 beta-mediated increase in MnSOD mRNA was dependent on new transcription, but was independent of de novo protein synthesis. Our data on the induction of the MnSOD gene by immune complexes and IL-1 beta could indicate an important role for MnSOD in the cellular defense against ROS toxicity in glomerular inflammation.
 ...
PMID:Heat-aggregated IgG and interleukin-1-beta stimulate manganese superoxide dismutase in mesangial cells. 877 77

The changes in red blood cell (RBC) lipid peroxidation [measured via the malonyl dialdehyde (MDA) concentration], reduced (GSH), and oxidized glutathione (GSSG) levels, hemoglobin (Hb) oxidation and antioxidant enzyme [catalase (Cat), glutathione peroxidase, and superoxide dismutase (SOD)] activities were studied in 45 pediatric patients with various glomerular diseases [minimal change nephrotic syndrome (MCNS) in relapse or in remission, lupus nephropathy (SLE), poststreptococcal glomerulonephritis (APSGN), IgA nephropathy (IGA gn)], and in 20 adult patients with IGA gn and also in 15 pediatric and 14 adult controls. The in vitro effects of hydrogen peroxide [acetyl phenylhydrazine (APH) test] on the GSH and Hb metabolisms were likewise investigated. There was an increased oxidative stress in MCNS with relapse, IGA gn, SLE gn, and APSGN, which could be detected in the GSH and Hb oxidation and in the lipid peroxidation on the peripheral RBC-s. The RBC SOD and Cat activities were significantly lower in all patients than in the controls. The RBC GSSG level was significantly elevated in all patients, with the exception of MCNS in remission. This stimulated a compensatory GSH production in MCNS with relapse and in IGA gn, but not in SLE or APSGN. The regeneration of GSH from GSSG was reduced in MCNS with relapse, SLE, and IGA gn, but not in APSGN. In remission, the GSH-GSSG redox system normalizes, but in vitro the APH test stimulates an intensive Hb oxidation. In conclusion, there is a correlation between the presence of active glomerular disease and the evidence of oxidative changes in the various parameters measured in peripheral RBCs.
 ...
PMID:Oxidative stress and antioxidant defense mechanism in glomerular diseases. 895 40

We evaluated the roles of reactive oxygen species and intrinsic antioxidant enzymes in the development of daunomycin (DM)-induced nephropathy in mice. A single dose of DM (20 mg/kg intravenously) induced proteinuria by day 7 and the nephrotic syndrome by day 14 in DM-sensitive strain (A/J) but not in DM-resistant strain (C57BL/6J) (B6). Renal cortical lipid peroxide levels in the A/J mice significantly increased at days 2, 4, and 7 after DM injection, whereas no increase was observed in the B6 mice. The resistance to DM in B6 mice was associated with higher activities in renal cortical superoxide dismutase and glutathione peroxidase. The administration of superoxide dismutase or of dimethylthiourea significantly suppressed the DM-induced proteinuria in the A/J mice. Four days of superoxide dismutase or dimethylthiourea administration suppressed the proteinuria. These findings suggested that murine DM-nephropathy appeared to be mediated by reactive oxygen species and that intrinsic antioxidant enzyme activities may play an important role in the susceptibility to DM-induced nephropathy in mice.
 ...
PMID:Roles of reactive oxygen species and antioxidant enzymes in murine daunomycin-induced nephropathy. 901 94

Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric acid) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin. Rats with nephrotic syndrome treated from the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.
 ...
PMID:The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats. 912 35

There is an individual susceptibility to diabetic nephropathy, and oxidative stress is believed to play an important role in the pathogenesis of diabetic complications. Active oxygen species induce antioxidant enzyme expression in tissues, an effect considered to be a defensive mechanism. To test whether altered intracellular antioxidant enzyme production might explain the predisposition to diabetic nephropathy, we studied the effect of long-term (12 weeks) exposure to normal (5 mmol/l) or high (22 mmol/l) glucose concentrations on fibroblast antioxidant enzyme gene expression and protein activity in type 1 diabetic patients with and without nephropathy, nondiabetic nephropathic patients, and nondiabetic control subjects. Under conditions of normal glucose concentration in the culture media, CuZnSuperoxide-dismutase, MnSuperoxide-dismutase, catalase, and glutathione-peroxidase activity and mRNA expression were not different among the four groups. Under high-glucose conditions, CuZnSuperoxide-dismutase mRNA and activity increased similarly in all groups (P < 0.001 vs. basal), whereas MnSuperoxide-dismutase did not change. In contrast, catalase mRNA and activity as well as glutathione-peroxidase mRNA and activity increased in fibroblasts from type 1 diabetic patients without nephropathy (P < 0.001), in fibroblasts from nondiabetic nephropathic patients (P < 0.001), and in fibroblasts from nondiabetic control subjects (P < 0.001), but not in fibroblasts from type 1 diabetic patients with nephropathy. Exposure to high glucose concentrations significantly increased lipid peroxidation in cells, higher levels being found in cells from diabetic patients with nephropathy (P < 0.001). These data, while confirming that exposure to high glucose concentrations induces an antioxidant defense in skin fibroblasts from normal subjects, demonstrate a failure of this defensive mechanism in cells from type 1 diabetic patients with nephropathy, whereas skin fibroblasts from diabetic patients without complications or from nondiabetic nephropathic patients have an intact antioxidant response to glucose-induced oxidative stress.
 ...
PMID:Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy. 1111 22

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.
 ...
PMID:Effect of hemodialysis on the oxidative stress and antioxidants. 1247 39

Recently, numerous studies have shown antioxidant actions of melatonin. Melatonin at both physiological and pharmacological levels stimulates glutathione peroxidase, glutathione reductase and superoxide dismutase activities in the brains of rats and chickens. This study was designed to evaluate the effect of melatonin on nephropathy and oxidative stress under constant light exposure. Nephropathy was induced by adriamycin administered in a single dose (25 mg kg(-1) b.w., i.p.). Melatonin was injected i.p. (1,000 microg kg(-1) b.w./day). Malondialdehyde, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione transferase, catalase and superoxide dismutase were determined in kidney. Urea, creatinine and total proteins in plasma and proteinuria were evaluated and melatonin was determined. Results show a decrease in melatonin levels. Similar effects occurred with the antioxidant enzyme activities and reduced glutathione. Likewise, adriamycin and constant light induced significant enhancement of malondialdehyde. All changes induced both by adriamycin and constant light were reverted to normal by melatonin administration. Constant light exposure was associated with an increase in oxidative stress and nephropathy induced by adriamycin. Treatment with melatonin decreased lipid peroxides, and permitted a recovery of reduced glutathione, scavenger enzyme activity and parameters of renal function.
 ...
PMID:Melatonin effect on renal oxidative stress under constant light exposure. 1257 19

Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2'-7' dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. A three times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy.
 ...
PMID:Changes in oxidative balance in rat pericytes exposed to diabetic conditions. 1509 Feb 67

In many diseases, including progressive renal disorders, tissue injury and pathological intracellular signaling events are dependent on oxidative stress. Glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that is highly expressed in the kidney and removes peroxides and peroxynitrite that can cause renal damage. Therefore, we examined whether this abundant renal antioxidant enzyme limits renal damage during the development of type 1 diabetic nephropathy. Wild-type (Gpx1+/+) and deficient (Gpx1-/-) mice were made diabetic by intraperitoneal injection of streptozotocin (100 mg/kg) on 2 consecutive days. Diabetic Gpx1+/+ and -/- mice with equivalent blood glucose levels (23 +/- 4 mM) were selected and examined after 4 mo of diabetes. Compared with normal mice, diabetic Gpx1+/+ and -/- mice had a two- to threefold increase in urine albumin excretion at 2 and 4 mo of diabetes. At 4 mo, diabetic Gpx1+/+ and -/- mice had equivalent levels of oxidative renal injury (increased kidney reactive oxygen species, kidney lipid peroxidation, urine isoprostanes, kidney deposition of advanced glycoxidation, and nitrosylation end products) and a similar degree of glomerular damage (hypertrophy, hypercellularity, sclerosis), tubular injury (apoptosis and vimentin expression), and renal fibrosis (myofibroblasts, collagen, TGF-beta excretion). A lack of Gpx1 was not compensated for by increased levels of catalase or other Gpx isoforms in diabetic kidneys. Contrary to expectations, this study showed that the high level of Gpx1 expressed in the kidney is not protective against the development of renal oxidative stress and nephropathy in a model of type 1 diabetes.
 ...
PMID:Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. 1582 46


1 2 3 Next >>