Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay-based biosensors. The implications of these results upon on-line analysis are discussed.
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PMID:Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin. 821 81

To examine the role of free radicals in diabetic cardiomyopathy, myocardial antioxidants as well as lipid peroxide content were examined in rats made diabetic with a single injection of streptozotocin (65 mg/kg i.v). At 4 wk, the left ventricular peak systolic (LVSP) as well as aortic pressures were depressed in the diabetic group. Hearts from diabetic animals showed about a 100% increase in thiobarbituric acid reactive substances (TBARS), indicating increased lipid peroxidation. This was accompanied by about a 50% decrease in superoxide dismutase (SOD) and 60% decrease in glutathione peroxidase (GSHPx) enzyme activities. Catalase activity in these hearts showed a small but significant increase. Treatment with probucol (10 mg/kg i.p., on alternate days), a known lipid-lowering drug with strong antioxidant properties, was initiated 1 d after the induction of diabetes and was continued for 4 wk. In probucol-treated diabetic animals, LVSP was not different from controls. Probucol treatment caused a small but significant improvement in serum insulin and decrease in glucose levels as well as increased myocardial SOD, GSHPx, and catalase activities with a concomitant decrease in TBARS in the diabetic animals. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit, and a better cardiac function due to treatment with probucol may be related to the improved insulin levels as well as maintenance of the antioxidant status of the heart.
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PMID:Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy. 874 20

We have previously used the comet assay to demonstrate that the nitric oxide donor 3-morpholinosydnonimine (SIN-1) produces DNA damage in rat islets of Langerhans and in the SV40-transformed insulin-secreting hamster cell line, HIT-T15. Damage is not prevented by the addition of superoxide dismutase (SOD). In the present study, we have compared SIN-1, which generates nitric oxide, superoxide anion and hydrogen peroxide, with two other nitric oxide donors, S-nitrosoglutathione (GSNO) and the tetra-iron-sulphur cluster nitrosyl, Roussin's black salt (RBS). We have used the comet assay as a highly sensitive method to measure DNA-damaging ability, and also measured inhibition of DNA synthesis and inhibition of insulin secretion. We have examined the effect of SOD and catalase on each of these endpoints in HIT-T15 cells following a 30-min exposure to the compounds (24 h for DNA synthesis). All compounds produced a significant dose-dependent increase in strand-breakage formation and all inhibited DNA synthesis and glucose-stimulated insulin secretion. RBS was the most potent. SOD did not reduce the responses observed with any of the compounds. Catalase largely prevented DNA strand breakage, inhibition of DNA synthesis and inhibition of insulin secretion by SIN-1, but had no effect on responses to GSNO or RBS. Addition of SOD together with catalase gave no greater protection against SIN-1 than catalase alone. The nitric oxide and superoxide anion produced by SIN-1 are though to combine to form highly reactive peroxynitrite. In addition, H2O2 may be formed in the presence of SIN-1 and may form hydroxyl radical in the presence of a transition metal, such as Fe2+. It appears that in insulin-secreting cells, the effects of SIN-1 are largely mediated by this latter mechanism. In contrast, GSNO and RBS appear to act by a different mechanism, not overtly involving reactive oxygen species. GSNO and H2O2 show no significant interaction in the induction of DNA strand breaks. Both nitric oxide and H2O2 are effective, directly or indirectly, as DNA strand-breaking agents, inhibitors of DNA synthesis and inhibitors of insulin secretion.
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PMID:Use of the comet assay to investigate possible interactions of nitric oxide and reactive oxygen species in the induction of DNA damage and inhibition of function in an insulin-secreting cell line. 920 24

Antioxidant enzyme expression was determined in rat pancreatic islets and RINm5F insulin-producing cells on the level of mRNA, protein, and enzyme activity in comparison with 11 other rat tissues. Although superoxide dismutase expression was in the range of 30% of the liver values, the expression of the hydrogen peroxide-inactivating enzymes catalase and glutathione peroxidase was extremely low, in the range of 5% of the liver. Pancreatic islets but not RINm5F cells expressed an additional phospholipid hydroperoxide glutathione peroxidase that exerted protective effects against lipid peroxidation of the plasma membrane. Regression analysis for mRNA and protein expression and enzyme activities from 12 rat tissues revealed that the mRNA levels determine the enzyme activities of the tissues. The induction of cellular stress by high glucose, high oxygen, and heat shock treatment did not affect antioxidant enzyme expression in rat pancreatic islets or in RINm5F cells. Thus insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression. Through stable transfection, however, we were able to increase catalase and glutathione peroxidase gene expression in RINm5F cells, resulting in enzyme activities more than 100-fold higher than in nontransfected controls. Catalase-transfected RINm5F cells showed a 10-fold greater resistance toward hydrogen peroxide toxicity, whereas glutathione peroxidase overexpression was much less effective. Thus inactivation of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin-producing cells. Overexpression of catalase may therefore be an effective means of preventing the toxic action of reactive oxygen species.
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PMID:Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. 935 19

Alloxan-induced diabetic rats were treated with insulin (i.p.) or with Capparis decidua powder as a hypoglycaemic agent mixed with diet. The effect was assessed on lipid peroxidation (LPO) and the antioxidant defense system in rat tissues. The increased levels of blood glucose in diabetes produce superoxide anions and hydroxyl radicals in the presence of transition metal ions which cause oxidative damage to cell membranes. The heart tissue showed an increased lipid peroxidation (LPO) in diabetic rats while no significant change was observed in the liver and kidney. The treatment with C. decidua lowered LPO in these tissues even more effectively than insulin-treated rats. The superoxide dismutase (SOD) activity increased in the heart and kidneys in the diabetic group of rats probably to increase dismutation of superoxide anions. However, treatment with C. decidua decreased SOD activity in the liver and kidney and was comparable to control rats. Catalase (CAT) activity was not significantly affected in any of the tissues in diabetic and insulin-treated animals, however, CAT activity markedly increased in tissues with C. decidua treatment. Total and Se-dependent glutathione peroxidase (GSH-Px) in the heart was markedly lowered in diabetic rats which recovered with insulin as well as with C. decidua treatment. The increase in GSH-Px and CAT activity with C. decidua treatment may lower H2O2 toxicity and reduce oxidative stress in diabetes. However, glutathione (GSH) content in the heart and kidney and glutathione reductase (GSH-R) activity in all the tissues studied increased in diabetic rats while treatment with insulin lowered GSH content and GSH-R activity in these tissues. The treatment with C. decidua also decreased GSH-R activity in the kidney and heart which resulted in the decrease in GSH content in these tissues. The changes such as the increase in kidney and heart SOD may be an adaptive response in order to neutralize superoxide anions. The increase in GSH content and GSH-R activity in the tissue are in response to neutralize superoxide anions and to counteract oxidative stress in diabetes. Glutathione S-transferase (GST) was not significantly affected in diabetic rat tissue, however, heart GST increased with antidiabetic treatments. The increase in glucose-6-phosphate dehydrogenase (G6PDH) in the kidney and heart of diabetic rats subsequently decreased with C. decidua treatment. The increase in G6PDH in tissues may increase NADPH generation required for GSH-R activity and GSH production. It is suggested that these changes initially counteract the oxidative stress in diabetes, however, a gradual decrease in the antioxidative process may be one of the factors which results in chronic diabetes. The data indicate that C. decidua may have potential use as an antidiabetic agent and in lowering oxidative stress in diabetes.
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PMID:Action of capparis decidua against alloxan-induced oxidative stress and diabetes in rat tissues. 936 67

BetaTC6-F7 cells like normal Beta cells were found to be highly sensitive to hydrogen peroxide and to possess very low levels of catalase. Therefore we tested whether overexpression of catalase could enhance resistance to hydrogen peroxide. Enzyme activity was increased forty fold by transient transfection of a catalase transgene. To assess protection from hydrogen peroxide a cotransfection method using a human growth hormone reporter gene was developed. Human growth hormone secretion was shown to be a suitable marker for insulin secretion since both hormones demonstrated virtually identical glucose dose response curves. Catalase transfection was found to provide significant protection against hydrogen peroxide indicating that low catalase may contribute to the sensitivity of cells to hydrogen peroxide.
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PMID:Catalase transfection decreases hydrogen peroxide toxicity in a pancreatic beta cell line. 955 56

Alloxan is known to induce diabetes in experimental animals through destruction of insulin-producing 3-cells of pancreas. The mechanism of DNA damage induced by alloxan was investigated using 32P-labeled human DNA fragments. Cu(II)-dependent DNA damage increased with the concentration of alloxan and NADH. Alloxan induced DNA cleavage frequently at thymine and cytosine residues in the presence of NADH and Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, almost completely inhibited DNA damage, suggesting the involvement of H2O2 and Cu(I). Alloxan induced Cu(II)-dependent production of 8-oxodG in calf thymus DNA in the presence of NADH. UV-visible and electron spin resonance (ESR) spectroscopic studies showed that superoxide anion radical and alloxan radical were generated by the reduction of alloxan by NADH, and also by the autoxidation of dialuric acid, the reduced form of alloxan. These results suggest that the copper-oxygen complex derived from the reaction of H2O2 with Cu(I) participates in Cu(II)-dependent DNA damage by alloxan plus NADH and dialuric acid. The mechanism of DNA damage is discussed in relation to diabetogenic action of alloxan.
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PMID:Metal-mediated DNA damage induced by diabetogenic alloxan in the presence of NADH. 974 96

One theory suggests that by maintaining the protein in an amorphous glassy sugar matrix, the physical hindrance encountered by the protein functions to stabilize it. Thus, the nature of the sugar/protein interaction is important as is the maintenance of the sugar in an amorphous form without any recrystallization. Moisture is known to function as a plasticizer and facilitate crystallization and thus loss of the amorphous state. We report the effect of cospray-drying with different proteins on the physical stability of lactose and mannitol. Particle sizing showed their suitability for inhalation, and the effect of exposure of the spray-dried products to moisture vapor was monitored gravimetrically. Bovine liver catalase, bovine pancreatic insulin, and bovine pancreatic ribonuclease A when individually cospray-dried with lactose showed no extensive initial crystallinity by powder X-ray diffraction, but proteins cospray-dried with mannitol generally showed evidence of mannitol component crystallinity. Catalase appeared to inhibit lactose crystallization from an amorphous matrix to a greater extent than insulin when exposed to short-term elevated humidity, but this difference was a kinetic feature. The hygroscopicities of the cospray-dried materials differed and indicated that each protein/sugar system required individual characterization to identify an optimal formulation.
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PMID:Water vapor sorption studies on the physical stability of a series of spray-dried protein/sugar powders for inhalation. 981 83

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

Pancreatic beta cells are sensitive to reactive oxygen species and this may play an important role in type 1 diabetes and during transplantation. Beta cells contain low levels of enzyme systems that protect against reactive oxygen species. The weakest link in their protection system is a deficiency in the ability to detoxify hydrogen peroxide by the enzymes glutathione peroxidase and catalase. We hypothesize that the deficit in the ability to dispose of reactive oxygen species is responsible for the unusual sensitivity of beta cells and that increasing protection will result in more resistant beta cells. To test these hypotheses we have produced transgenic mice with increased beta cell levels of catalase. Seven lines of catalase transgenic mice were produced using the insulin promoter to direct pancreatic beta cell specific expression. Catalase activity in islets from these mice was increased by as much as 50-fold. Northern blot analysis of several tissues indicated that overexpression was specific to the pancreatic islet. Catalase overexpression had no detrimental effects on islet function. To test whether increased catalase activity could protect the transgenic islets we exposed them to hydrogen peroxide, streptozocin, and interleukin-1beta. Fifty-fold overexpression of catalase produced marked protection of islet insulin secretion against hydrogen peroxide and significantly reduced the diabetogenic effect of streptozocin in vivo. However, catalase overexpression did not provide protection against interleukin-1beta toxicity and did not alter the effects of syngeneic and allogenic transplantation on islet insulin content. Our results indicate that in the pancreatic beta cell overexpression of catalase is protective against some beta cell toxins and is compatible with normal function.
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PMID:Overexpression of catalase provides partial protection to transgenic mouse beta cells. 1051 87


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