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)

The insulin signaling pathway is activated by tyrosine phosphorylation of the insulin receptor and key post-receptor substrate proteins and balanced by the action of specific protein-tyrosine phosphatases (PTPases). PTPase activity, in turn, is highly regulated in vivo by oxidation/reduction reactions involving the cysteine thiol moiety required for catalysis. Here we show that insulin stimulation generates a burst of intracellular H(2)O(2) in insulin-sensitive hepatoma and adipose cells that is associated with reversible oxidative inhibition of up to 62% of overall cellular PTPase activity, as measured by a novel method using strictly anaerobic conditions. The specific activity of immunoprecipitated PTP1B, a PTPase homolog implicated in the regulation of insulin signaling, was also strongly inhibited by up to 88% following insulin stimulation. Catalase pretreatment abolished the insulin-stimulated production of H(2)O(2) as well as the inhibition of cellular PTPases, including PTP1B, and was associated with reduced insulin-stimulated tyrosine phosphorylation of its receptor and high M(r) insulin receptor substrate (IRS) proteins. These data provide compelling new evidence for a redox signal that enhances the early insulin-stimulated cascade of tyrosine phosphorylation by oxidative inactivation of PTP1B and possibly other tyrosine phosphatases.
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PMID:Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. 1129 36

Tumor necrosis factor-alpha (TNF-alpha) is involved in insulin resistance. Since the fact that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit the induction of TNF-alpha by phorbol ester, but not by lipopolysaccharide (LPS), suggests two pathways to induce TNF-alpha, we investigated the mechanisms of glycated human albumin (GHA)- or phorbol ester-induced TNF-alpha in THP-1 cells. GHA induced TNF-alpha release in differentiated THP-1 cells, while phorbol ester induced TNF-alpha release in undifferentiated cells but did not induce TNF-alpha in differentiated cells. Forskolin (adenylate cyclase activator) affected more the GHA-induced TNF-alpha release than the phorbol 12-myristate 13-acetate (PMA)-induced one in undifferentiated cells. Staurosporine [protein kinase-C (PK-C) inhibitor] and PD98059 [mitogen-activated protein kinase inhibitor (MAPK)] only partially inhibited GHA-induced TNF-alpha. Catalase completely inhibited GHA-induced TNF-alpha release; however, superoxide dismutase (SOD) had no effect. These results suggest at least two pathways to induce TNF-alpha (phorbol ester- and GHA-dependent ways) and that GHA-induced TNF-alpha release is through predominantly catalase-dependent way in differentiated THP-1 cells.
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PMID:Tumor necrosis factor-alpha is induced through phorbol ester--and glycated human albumin-dependent pathway in THP-1 cells. 1136 14

Identification of longevity mutants is crucial for genetic approach to dissect the molecular mechanism of aging and longevity determination. In Drosophila melanogaster, several mutations have been shown to extend the longevity: methuselah encoding a putative G-protein coupled receptor, Indy encoding a sodium dicarboxylate cotransporter, chico encoding insulin receptor substrate, and InR encoding the insulin-like receptor. Extended longevity phenotypes were also observed in transgenic flies overexpressing antioxidant enzymes, Cu/Zn superoxide dismutase and Catalase, Cu/Zn SOD only, or a molecular chaperone, hsp70. Pleiotropism of mutations is a limitation associated with conventional mutagenesis for efficient detection of longevity determination genes. Using a conditional misexpression system, we identified Drosophila POSH (DPOSH), a scaffold protein containing RING finger and four SH3 domains, whose ubiquitous overexpression in adult stage extends the longevity. Neural-specific overexpression of DPOSH is sufficient to extend the longevity, whereas overexpression in non-neural tissues during development induces apoptosis through activation of JNK/SAPK pathway.
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PMID:Longevity determination genes in Drosophila melanogaster. 1247 Aug 91

Insulin-producing cells show very low activity levels of the cytoprotective enzymes catalase, glutathione peroxidase, and superoxide dismutase. This weak antioxidative defense status has been considered a major feature of the poor resistance against oxidative stress. Therefore, we analyzed the protective effect of a combined overexpression of Cu,ZnSOD or MnSOD together with different levels of catalase. Catalase alone was able to increase the resistance of transfected RINm5F insulin-producing tissue culture cells against H(2)O(2) and HX/XO, but no protection was seen in the case of menadione. In combination with an increase of the MnSOD or Cu,ZnSOD expression, the protective action of catalase overexpression could be further increased and extended to the toxicity of menadione. Thus, optimal protection of insulin-producing cells against oxidative stress-mediated toxicity requires a combined overexpression of both superoxide- and hydrogen peroxide-inactivating enzymes. This treatment can compensate for the constitutively low level of antioxidant enzyme expression in insulin-producing cells and may provide an improved protection in situations of free radical-mediated destruction of pancreatic beta cells in the process of autoimmune diabetes development.
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PMID:Sequential inactivation of reactive oxygen species by combined overexpression of SOD isoforms and catalase in insulin-producing cells. 1263 45

Pancreatic beta-cells have low activities of the antioxidant enzyme catalase. Nitric oxide interacts with the haem group of catalase inhibiting its activity. We have studied the activity of catalase in beta-cells under conditions mimicking prediabetes and in which nitric oxide is generated from cytokine treatment in vitro. We also studied whether there is regulation of catalase enzyme activity by nitric oxide at the protein or gene expression level. RINm5F insulin-producing cells, treated for 24 h with cytokines, showed increased medium nitrite production (17+/-2.2 vs 0.3+/-0.2 pmol/ micro g protein) and significantly decreased cellular catalase activity (42.4+/-4.5%) compared with control cells. A similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or human pancreatic islets of Langerhans. Catalase activity was also suppressed by the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta-NO) and this inhibition was reversible. The inhibition of catalase activity by cytokines in RINm5F cells was significantly reversed by the addition of the nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3-(aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be unchanged in cytokine- or Deta-NO-treated RINm5F cells, while mRNA expression was marginally increased. We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine- or nitric oxide-induced cell killing.
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PMID:Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells. 1466 11

Two basic models of alcoholic liver disease pathogenesis exist, one in vivo and one in vitro. To justify the in vitro model, evidence is needed to show that it stimulates the in vivo model. Therefore, changes in gene expression caused by high ethanol level were compared using the two models. Many functional pathways were upregulated in both models. These included the insulin signaling pathway, TGFbeta signaling pathway, apoptosis, MAPK signaling pathway, wnt signaling pathway and apoptosis. Differences were found in the fatty acids synthesis pathway, which was upregulated in vivo; and glycosylation enzymes which were downregulated in vivo. Also, downregulated in vitro were beta oxidation by mitochondria and translation factors. Catalase and superoxide dismutase in mitochondria were upregulated in vitro. These two enzymes have antioxidant effects. In summary, remarkably similar responses to high alcohol levels in the form of changes in gene expression pathways were found in the in vivo and in vitro models tested.
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PMID:Gene expression patterns of the liver in response to alcohol: in vivo and in vitro models compared. 1677 Aug 50

Intracellular Ca2+ homeostasis in platelets of patients with non-insulin-dependent diabetes mellitus (NIDDM) has been reported to be altered, leading to an increased adhesiveness and spontaneous aggregation. Among the disturbed Ca2+ mechanism in platelets from NIDDM subjects, a reduced Ca2+ extrusion by the plasma membrane Ca2+-ATPase (PMCA) is especially relevant, maintaining an elevated cytosolic free Ca2+ concentration that results in platelet hypersensitivity. Here we show that treatment of platelets from NIDDM patients with 300 U/mL catalase or 5 mM D-mannitol, which prevent H2O2- and hydroxyl radicals-mediated oxidative stress, respectively, increases Ca2+ extrusion after treatment with thapsigargin (TG) plus ionomycin (Iono). In contrast, 1 mM trolox, a scavenger of ONOO-, did not alter TG + Iono-induced response. Catalase and D-mannitol reversed the enhanced tyrosine phosphorylation of PMCA induced by TG + Iono in NIDDM patients. These findings open up new horizon for the development of therapeutic strategies to palliate cardiovascular disorders in NIDDM.
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PMID:Endogenously generated reactive oxygen species reduce PMCA activity in platelets from patients with non-insulin-dependent diabetes mellitus. 1692 98

Extra-virgin olive oil (OO) is becoming more important in daily diets due to its beneficial effects on health, most of which are because of its antioxidant content. We studied the antioxidant activity and mechanisms of an extra-virgin OO that is rich in phenolics on pancreatic islets and liver in control mice (CTL) fed a nonpurified diet and in mice supplemented with 50 microL/d sunflower oil (SO) or 50 microL/d extra-virgin OO for 4 d. Plasma hydroxytyrosol concentration was determined by HPLC-diode array detector. Plasma antioxidant capacity, enzymatic activities, and lipid peroxidation were measured by spectrophotometry. Islet function was studied by measuring insulin release. Islet cell gene expression was examined using quantitative RT-PCR. The plasma hydroxytyrosol concentration was greater in OO mice than in CTL or SO mice (P < 0.05) and was greater in SO mice than in CTL mice. The ratio of reduced:oxidized glutathione and the antioxidant capacity in plasma was greater in OO mice than in CTL or SO mice (P < 0.05) and higher in SO mice than in CTL mice. Glucose-stimulated insulin secretion was greater in OO mice than in CTL or SO mice (P < 0.05) and was also higher in SO mice than in CTL mice. Protection against liver cell and beta cell membrane lipid peroxidation was greater in OO mice than in CTL or SO mice (P < 0.05) and was greater in SO mice than in CTL mice. Catalase (CAT) expression in the islet of Langerhans was higher in OO mice than in CTL mice and SO mice (P < 0.05). The CAT and glutathione peroxidase 1 activities in the islet of Langerhans were 25% greater in OO mice than in CTL mice and higher than in SO mice (P < 0.05) and they were greater in SO mice than in CTL mice. These results indicate that, in metabolic tissues, protection by extra-virgin OO against oxidative stress occurs primarily through a direct antioxidant effect as well as through an indirect mechanism that involves greater expression and activity of certain enzymes with antioxidant activities.
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PMID:An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice. 1849 36

Mitochondrial reactive oxygen species have been implicated in both diabetic complications and the progression of the underlying diabetic state. However, it is not clear whether mitochondria of diabetic origin are intrinsically altered to generate excess reactive oxygen species independent of the surrounding diabetic milieu. Mitochondria were isolated from gastrocnemius, heart, and liver of 2-wk and 2-month streptozotocin diabetic rats and controls. We rigidly quantified mitochondrial superoxide, respiration and ATP production, respiratory coupling, the expression of several proteins with antioxidant properties, and the redox state of glutathione. Both fluorescent assessment and electron paramagnetic spectroscopy revealed that superoxide production was unchanged or reduced in the 2-month diabetic mitochondria compared with controls. Kinetic analysis of the proton leak showed that diabetic heart and muscle mitochondria were actually more coupled compared with control despite an approximate 2- to 4-fold increase in uncoupling protein-3 content. Adenine nucleotide translocator type 1 expression was reduced by approximately 50% in diabetic muscle mitochondria. Catalase was significantly up-regulated in muscle and heart tissue and in heart mitochondria, whereas glutathione peroxidase expression was increased in liver mitochondria of diabetic rats. We conclude that gastrocnemius, heart, and liver mitochondria of streptozotocin diabetic rats are not irrevocably altered toward excess superoxide production either by complex I or complex III. Moreover, gastrocnemius and heart mitochondria demonstrate increased, not decreased, respiratory coupling. Mitochondria of insulin-deficient diabetic rats do show signs of adaptation to antecedent oxidative stress manifested as tissue-specific enzyme and uncoupling protein expression but remain remarkably robust with respect to superoxide production.
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PMID:Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats. 1877 40

Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer's, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson's disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer's peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P << 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes - methionine cycle, insulin correlation - are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.
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PMID:Systemic oxidative stress associated with the neurological diseases of aging. 1948 52


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