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)

Rat kidney homogenates metabolize N6-trimethyl-lysine to N-trimethylammoniobutyrate, but not to carnitine. The first step in this conversion is the hydroxylation of trimethyl-lysine to form 3-hydroxy-N6-trimethyl-lysine. An assay system was developed in which hydroxylation of trimethyl-lysine is linear with respect to both time and homogenate protein concentration. The rate is 5 nmol of 3-hydroxy-N6-trimethyl-lysine formed/min per mg of homogenate protein. The cofactors required are ascorbate, alpha-oxoglutarate, FeSO4, and O2. Catalase and dithiothreitol give a 20% stimulation. Ca2+ produces a 2-fold increase in specific activity and cannot be replaced by Mg2+, Mn2+ or Zn2+. These last three bivalent cations lead to a decreased activity. Subcellular distribution studies demonstrate that trimethyl-lysine hydroxylase activity parallels the distribution profile of succinate dehydrogenase and citrate synthase. Thus trimethyl-lysine hydroxylase has a mitochondrial localization. Distribution of trimethyl-lysine hydroxylase activity between cortex and medulla of kidney if 67 and 33% respectively, similar to mitochondrial distribution.
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PMID:Carnitine biosynthesis. Hydroxylation of N6-trimethyl-lysine to 3-hydroxy-N6-trimethyl-lysine. 677 70

Homogenates of the posterior latissimus dorsi muscle, a phasic muscle, were fractionated by a one-step zonal centrifugation technique into four major organelle populations and cytoplasmic constituents. These were: (1) Plasma membrane fragments with a modal equilibrium density of 1.10 and containing 5'-nucleotidase, alkaline phosphodiesterase, p-nitrophenylphosphatase and acid phosphatase (beta-glycerophosphate was used as the substrate). (2) Sarcoplasmic reticular fragments which could be further subdivided into calcium transport vesicles, with a model equilibrium density of 1.16, that exhibited calcium uptake; K+-ATPase; leucyl-bet-naphthylamidase; acid phosphodiesterase; acid phosphatase (using cytidine monophosphate as the substrate); and sarcoplasmic reticular lysosomes, with a model equilibrium density of 1.18, possessing dipeptidyl-aminopeptidase II, cathepsin D, alpha-glucosidase, N-acetyl-beta-glucosaminidase, and NADH oxidase activity. (3) Mitochondria with a modal equilibrium density of 1.21. (4) Catalase-containing vesicles with a modal equilibrium density of 1.22; and cytoplasmic constituents (modal density of 1.25) with phosphorylase, pyruvate kinase, myosin-ATPase, aldolase, and protein and RNA content. The purity of these organelles was equal to or better than previous efforts, with a 30-fold purification achieved for 5'-nucleotidase and alkaline phosphodiesterase. These results lend support to the hypothesis that the sarcoplasmic reticulum of phasic muscle, in addition to its specialized role in excitation-contraction coupling, represents a multifunctional membrane system, and that, similar to the smooth endoplasmic reticulum of other cells, it includes some membrane-bound lysosomal enzymes and NADH oxidase.
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PMID:Isopycnic-zonal centrifugation of plasma membrane, sarcoplasmic reticular fragments, lysosomes, and cytoplasmic proteins from phasic skeletal muscle. 721 87

We present in this report the characteristics of the damage induced by 6-hydroxydopamine and H2O2 on bovine chromaffin cells in primary culture. Cytotoxicity was quantified using catecholamine cell contents, lactate dehydrogenase (LDH) release, trypan blue exclusion and morphological appearance. An excellent correlation between these four parameters was found. The cytotoxic effects of 6-hydroxydopamine were Ca(2+)-independent. In spite of this, the Ca2+ channel antagonists R56865 (N-[1-(4-(fluorophenoxy)butyl)]-4-piperidinyl-N-methyl-2-benzo-thiazo lamine) lidoflazine exhibited marked cytoprotective effects against both 6-hydroxydopamine and H2O2. The selective dopamine uptake blocker, bupropion, increased the viability of 6-hydroxydopamine and H2O2-treated cells from 20% to around 80%. Catalase drastically protected against the cytotoxic effects of 6-hydroxydopamine and H2O2. In contrast, desferrioxamine gave better protection against H2O2 cytotoxicity; glutathione and N-acetylcysteine only afforded substantial protection against 6-hydroxydopamine. Three main conclusions emerge from this study. (1st) 6-Hydroxydopamine causes chromaffin cell damage via a mechanism probably related to the production of free radicals, but unrelated to Ca2+ ions. Cytoprotection afforded by R56865 and lidoflazine must be unrelated to their Ca2+ antagonist properties. This suggests a novel component in the cytoprotective mechanism of action of these drugs. (2nd) The strong cytoprotective effects of bupropion seem to be unrelated to its ability to block the plasmalemmal dopamine carrier. (3rd) Bovine adrenal chromaffin cells in primary cultures are a suitable model for adult neurons to study the basic mechanism of cell damage, and to screen new drugs with putative neuroprotective properties.
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PMID:Pharmacological protection against the cytotoxicity induced by 6-hydroxydopamine and H2O2 in chromaffin cells. 767 8

Effects of hypoxia-reoxygenation (H-R) on myocytes isolated from 10 week hypertrophied and sham control rat hearts were studied. Myocyte hypertrophy was indicated by an increase in cell size. Superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities were significantly higher and lipid peroxidation (TBARS) was lower in hypertrophied myocytes prior to any H-R. Hypertrophied myocyte population showed significantly less damage to cell morphology due to H-R. In sham as well as hypertrophied myocytes, Na+ and Ca2+ contents were increased by H-R, but Ca2+ accumulation was significantly less in the hypertrophied myocytes. Both SOD and GSHPx activities were depressed by the oxidative stress in the sham myocytes whereas these activities were not significantly changed in the hypertrophied myocytes. Catalase activity in the prehypoxic sham and hypertrophied myocytes was comparable and this activity did not change during H-R. There was a significant increase in lipid peroxidation due to H-R but this change was less in hypertrophied myocytes. This study shows less vulnerability of hypertrophied myocytes to oxidative stress and an increase in endogenous antioxidant reserve may have an important role in mediating this protection.
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PMID:Endogenous antioxidants in isolated hypertrophied cardiac myocytes and hypoxia-reoxygenation injury. 776 Mar 50

Artemisinin is an effective antimalarial agent, and its action on the malarial parasite is suggested to be mediated by oxidative processes. Since malarial parasites contain a high concentration of hemin, and hemin may induce the formation of reactive oxygen species, we investigated the interaction of artemisinin, iron and hemin. We used erythrocyte membrane-bound Ca2+ pump ATPase (basal) and calmodulin (CaM)-activated Ca2+ pump ATPase as our model. Membranes were incubated with artemisinin in the presence or absence of iron-ascorbate or hemin at 37 degrees for 1 hr. Following incubation, ATPase activity was measured. Our results showed that artemisinin (500 microM) had no effect on ATPase activities. However, artemisinin enhanced the inhibitory effect of iron (50 microM)-ascorbate (500 microM) on ATPase activity (46.3 +/- 3.9 vs 63 +/- 2.1% for basal; 57.2 +/- 2.5 vs 74.8 +/- 2.1% for CaM-activated). Desferrioxamine (DFO, 200 microM) blocked significantly the effect of iron-ascorbate-artemisinin on ATPases (P < 0.01). Hemin inhibited ATPase activity in a concentration-dependent fashion. Artemisinin enhanced hemin (10 microM)-induced inhibition of basal (36.0 +/- 6.0 vs 73.7 +/- 3.0%) and CaM-activated Ca2+ pump ATPase (31.6 +/- 2.8 vs 70.0 +/- 1.5%). Iron chelators (DFO, ferene, 8-hydroxyquinoline, 1,10-phenanthroline, and 1,2-dimethyl-3-hydroxypyrid-4-one) had no effect on artemisinin plus hemin-induced enzyme inhibition. Catalase (2000 U/mL) had a minor effect on the artemisinin-hemin or hemin-mediated effect. Thiourea (1 mM) had no effect. However, superoxide dismutase (500 U/mL) and dithiothreitol blocked artemisinin-hemin or hemin-mediated ATPase inhibition significantly (P < 0.001). In conclusion, these results suggest that, in our model, artemisinin enhances the damage of hemin-induced ATPases via oxidation of thiol groups on the enzymes. Free iron or hydroxyl radical does not seem to be involved. This interaction between artemisinin and hemin may contribute to the antimalarial action of artemisinin against malarial parasites.
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PMID:Enhancement of hemin-induced membrane damage by artemisinin. 808 Apr 46

There is evidence that reperfusion injury of cardiac tissue may be caused by the generation of oxygen-derived free radicals and oxidants and by the induction of intracellular calcium overload, although the relation between these two mechanisms of injury is uncertain. In addition, the relation between the types of cellular injury and specific active species is unclear. In an attempt to resolve these problems, we investigated the effects of oxygen radicals and oxidants, which are purportedly generated during reperfusion after prolonged ischemia, and various antioxidants on contractility and morphology of cultured fetal mouse cardiac myocytes. Xanthine oxidase in the presence of xanthine, H2O2, HOCl, and NH2Cl induced cessation of spontaneous beating followed by cessation of electrical stimulation-elicited beating but did not induce an increase in [Ca2+]i. After prolonged incubation with xanthine oxidase + xanthine and H2O2, the cardiac myocytes showed morphological degeneration (at least 80% of the cells developed hypercontraction) with a concomitant increase in [Ca2+]i. These observations suggest that contractile impairment does not result in an increase of [Ca2+]i, but hypercontraction does. Catalase, but not superoxide dismutase, protected the cultured cardiac myocytes against xanthine oxidase + xanthine- and H2O2-induced contractile and morphological impairment. In the light of this observation, we hypothesize that the superoxide anion is not responsible for these types of impairment. Addition of dimethylthiourea (an .OH scavenger) and intracellular preloading with deferoxamine (an iron chelator) protected the myocytes against H2O2-induced contractile and morphological damage, but intracellular preloading with iron enhanced it. These observations led us to hypothesize that intracellularly generated .OH may be a mediator of H2O2-induced injury to cultured cardiac myocytes. In addition, we observed that H2O2 itself induced cessation of spontaneous but not electrical stimulation-elicited beating.
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PMID:Contractile and morphological impairment of cultured fetal mouse myocytes induced by oxygen radicals and oxidants. Correlation with intracellular Ca2+ concentration. 839 8

Oxygen free radicals are highly toxic end products of the cellular oxidative metabolism that are scavenged by antioxidative systems such as superoxide dismutase and catalase. Previous studies have suggested that oxygen free radicals may play a role in the pathophysiology of acute pancreatitis. The present study was designed to determine the effect of catalase on experimental acute pancreatitis in the rat. Rats were given either saline or enterokinase by the intraductal pancreatic route. Catalase was given intraperitoneally at doses of 80, 160 and 320 mg/kg. Administration of saline resulted in mild acute pancreatitis. In contrast, administration of enterokinase resulted in oedema, haemorrhage and necrosis of the pancreas. Catalase had no effect when given at 80 mg/kg; at 160 mg/kg, an improvement at the ultrastructural level was noted, whereas at 320 mg/kg, a change in serum calcium level was found. Our studies suggest that intraperitoneal administration of catalase slightly improves the outcome of experimental acute pancreatitis in the rat.
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PMID:[Effect of catalase on acute experimental pancreatitis in rats]. 847 46

Endrin, a poly-halogenated cyclic hydrocarbon, induces hepatic lipid peroxidation, modulates calcium homeostasis, decreases membrane fluidity, and increases nuclear DNA damage. Little information is available on the neurotoxicity of endrin. The effects of endrin on lipid peroxidation, DNA damage, and regional distribution of catalase activity were assessed in rat brain and liver 24 h following an acute oral dose of 4.5 mg endrin/kg. Lipid peroxidation associated with whole brain mitochondria increased 2.4-fold, whereas microsomal lipid peroxidation increased 2.8-fold following endrin administration. Lipid peroxidation also increased 2.0-fold both in hepatic mitochondria and microsomes. Catalase activity decreased 24% in the hypothalamus, 23% in the cortex, 38% in the cerebellum, and 11% in the brain stem in response to endrin. A 4.3-fold increase in brain nuclear DNA-single strand breaks (SSB) was observed in endrin-treated rats. Pretreatment of rats intraperitoneally with the lazaroid U74389F (16-desmethyl tirilazad) (10 mg/kg in two doses) attenuated the biochemical consequences of endrin-induced oxidative stress. The administration of U74389F in citrate buffer (pH 3.8) provided better protection than administering the lazaroid in corn oil, decreasing endrin-induced lipid peroxidation by 50-80% and DNA-SSB by approximately 72% in liver and 85% in brain, while ameliorating the suppressed catalase activity. The data suggest an involvement of an oxidative stress in the neurotoxicity and hepatotoxicity induced by endrin, which can be attenuated by the lazaroid U74389F.
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PMID:Protective effects of lazaroid U74389F (16-desmethyl tirilazad) on endrin-induced lipid peroxidation and DNA damage in brain and liver and regional distribution of catalase activity in rat brain. 858 61

Cross-linking B cell antigen receptor (BCR) elicits early signal transduction events, including activation of protein tyrosine kinases, phosphorylation of receptor components, activation of phospholipase C-gamma (PLC-gamma), and increases in intracellular free Ca2+. In this article, we report that cross-linking the BCR led to a rapid translocation of cytosolic protein tyrosine phosphatase (PTP) 1C to the particulate fraction, where it became associated with a 140-150-kD tyrosyl-phosphorylated protein. Western blotting analysis identified this 140-150-kD protein to be CD22. The association of PTP-1C with CD22 was mediated by the NH2-terminal Src homology 2 (SH2) domain of PTP-1C. Complexes of either CD22/PTP-1C/Syk/PLC-gamma(1) could be isolated from B cells stimulated by BCR engagement or a mixture of hydrogen peroxidase and sodium orthovanadate, respectively. The binding of PLC-gamma(1) and Syk to tyrosyl-phosphorylated CD22 was mediated by the NH2-terminal SH2 domain of PLC-gamma(1) and the COOH-terminal SH2 domain of Syk, respectively. These observations suggest that tyrosyl-phosphorylated CD22 may downmodulate the activity of this complex by dephosphorylation of CD22, Syk, and/or PLC-gamma(1). Transient expression of CD22 and a null mutant of PTP-1C (PTP-1CM) in COS cells resulted in an increase in tyrosyl phosphorylation of CD22 and its interaction with PTP-1CM. By contrast, CD22 was not tyrosyl phosphorylated or associated with PTP-1CM in the presence of wild-type PTP-1C. These results suggest that tyrosyl-phosphorylated CD22 may be a substrate for PTP-1C regulates tyrosyl phosphorylation of CD22.
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PMID:CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation. 862 66

H2O2 and other reduced oxygen species have been proposed as activators of the transcription factor, NF Kappa B. Stimulated macrophages produce superoxide and H2O2 (the respiratory burst). We tested the hypothesis that production of these species could serve as part of the NF Kappa B activation pathway in rat alveolar macrophages and the J774A.1 mouse monocyte/macrophage cell line. Phorbol myristate acetate (PMA) and ADP, which stimulate the respiratory burst, caused NF Kappa B activation in both cells. Catalase abolished NF kappa B activation, while superoxide dismutase produced little inhibition. Thus, H2O2 was the principal agent of respiratory burst-associated NF kappa B activation. Abolition of NF kappa B activation by catalase also suggested that intermediate signaling pathways, such as protein kinase C activation or intracellular free calcium elevation must not be involved. Exogenous H2O2 added as a bolus > or = 50 microM (> or = 50 nmol/10(6) macrophages) also activated NF kappa B in macrophages. Nevertheless, the maximum endogenous production of H2O2 by stimulated alveolar macrophages during a 30-min incubation was < or = 1.3 nmol H2O2/10(6) cells for PMA stimulation and < or = 0.2 nmol H2O2/10(6) cells for ADP stimulation. Thus, relatively little endogenous H2O2 generation was required to produce NF kappa B activation compared to the required amount of exogenous H2O2. As H2O2 rapidly diffuses and is consumed, these results suggest that the site of action for endogenously generated H2O2 is probably close to its origin, the plasma membrane.
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PMID:Activation of NF kappa B by the respiratory burst of macrophages. 916 12


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