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 nature of the compartmentalization of catalase in human myeloid cells is an unresolved issue. Using a rabbit polyclonal antibody specific for catalase, indirect immunocytofluorescence of immature leukemic promyelocytes (HL-60 cells) showed a pattern of small, sharp, punctate staining in the cytoplasm of all cells, while mature neutrophils showed a larger diffuse, flocculent pattern of cytoplasmic staining. Differential centrifugation of nitrogen cavitates of HL-60 cells indicated that the putative catalase-containing compartment was relatively fragile compared with the compartment(s) that contained myeloperoxidase (MPO), beta-hexosaminidase, beta-glucuronidase, and lysosomal alpha-mannosidase activities. Parallel studies using dimethylsulfoxide (DMSO)-induced HL-60 cells and mature neutrophils showed that, in the course of differentiation, there was an apparent shift in the localization of catalase from the granule fraction to the cytosolic fraction. Percoll-sucrose density gradient centrifugation of HL-60 cell cavitates showed a catalase-containing compartment with a mean peak density (1.05 g/mL) significantly lower than that of the major myeloperoxidase-containing compartment (1.08 g/mL); in mature neutrophils, catalase activity comigrated with lactate dehydrogenase (LDH) activity. Catalase in isolated fractions was protected from proteolysis in the absence, but not in the presence, of 0.1% Triton X-100. Digitonin titration experiments confirmed the compartmentalized nature of catalase in immature HL-60 cells and were consistent with a cytosolic localization in mature neutrophils. Ultrastructural localization of catalase by Protein A-gold immunocytochemistry demonstrated four to six catalase-containing compartments in all HL-60 cell profiles. In mature neutrophils, catalase was localized primarily in the cytoplasmic matrix, although in fewer than 2% of the cell profiles, one to two catalase-containing compartments were observed. The changes in catalase localization that occur during myeloid differentiation appear to be similar to the changes that occur during erythroid and megakaryocytic differentiation, and may have potential clinical significance in the classification of acute leukemia and in the development of drug resistance.
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PMID:Changes in the localization of catalase during differentiation of neutrophilic granulocytes. 816 45

Accumulating evidence demonstrates that oxidative damage is one of the underlying mechanisms to the cytotoxicity and carcinogenicity of AFB1. The main objective of this study is to show that AFB1 increases reactive oxygen species (ROS) formation in hepatocytes. The ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS. It was found that AFB1 exposure significantly enhanced DCF fluorescence formation in cultured rat hepatocytes. A dose-response of AFB1 was also observed within the range of 10 nM to 1000 nM. Catalase (CAT) was able to completely prevent the increase of DCF fluorescence in AFB1-treated cells in a dose-dependent manner (from 500 to 2000 U/ml). Moreover, the significant inhibitory effects of desferrioxamine (DFO) and dimethyl sulfoxide (DMSO) on DCF fluorescence formation were also observed in both control and AFB1-treated hepatocytes. Therefore, results from the present study provide in vitro evidence indicating the generation of ROS in cultured rat hepatocytes caused by AFB1 exposure. It is postulated that the metabolic process of AFB1 by cytochrome P450 might be the possible source of the elevated ROS level in AFB1-treated hepatocytes. The enhanced level of ROS may be responsible for the oxidative damage caused by AFB1, which may ultimately contribute to the cytotoxic and carcinogenic effects of AFB1.
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PMID:Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1. 881 28

In an accompanying manuscript, it was shown that the cartilage chondrolytic activities of fibronectin fragments (Fn-f), which are mediated through catabolic cytokines such as TNF-alpha, IL-1 and IL-6, could be suppressed by anti-oxidants (AOs). The AOs neutralized reactive oxygen species (ROS) which are known to mediate catabolic cytokine action. The objective in this work was to test whether AOs would promote restoration of proteoglycan (PG) in Fn-f treated cartilage, since under normal culturing conditions, PG is not restored after removal of the Fn-f. Cartilage was first cultured with an amino-terminal 29-kDa Fn-f to cause loss of about half of the total PG and then treated with NAC (1 and 10 mM) or glutathione (10 microM) or DMSO (0.1 or 1%). Treatment with NAC and glutathione maximally caused restoration of PG within 14 days to normal or supernormal levels, while DMSO was less effective. Catalase, but not superoxide dismutase, enhanced PG content to a small but significant extent. The restoration of PG in Fn-f treated cartilage occurred throughout the full depth of the cartilage slices as shown by histochemical analysis. However, removal of the AO allowed a subsequent decrease in PG content suggesting that the AOs had not blocked cytokine expression but had merely suppressed cytokine activities. Addition of NAC to IL-1 treated cartilage promoted a restoration of PG, while addition to chymopapain or trypsin treated cartilage was not very effective, suggesting that the effect of AOs requires a cytokine driven damage system. We conclude that the AOs promote a restoration of PG in the Fn-f treated cartilage by suppressing the effects of catabolic cytokines. The data suggest a potential for AOs in reversing tissue damage caused by cytokines.
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PMID:Fibronectin fragment mediated cartilage chondrolysis. II. Reparative effects of anti-oxidants. 895 Feb

We examined the effects of antioxidants, anti-inflammatory drugs, and histamine antagonists on auricular inflammation and retinal degeneration induced by the phototoxicity of sparfloxacin (SPFX), a quinolone antibacterial agent. Catalase (CAT), dimethyl sulfoxide (DMS0), dexamethasone (DM), indomethacin (IM), phenidone (PD), AA-861 (AA), pyrilamine maleate (PY), or cimetidine (CM) was continuously administered to female Balb/c mice using microosmotic pumps for 72 hr and intraperitoneally once before SPFX administration. The mice were given a single oral administration of 50 or 100 mg/kg SPFX and irradiated with ultraviolet-A (UVA) light at 1.5 mW/cm(2) for 4 hr. SPFX administration plus UVA irradiation induced thickening and inflammation of the auricular skin and retinal degeneration in the eye. CAT and DMS0 significantly inhibited the auricular thickening only 4 hr after SPFX administration. DM, IM, and PD also inhibited this toxicity from 4 to 48 or 72 hr. On the other hand, PY and CM showed no effect on this change. With regard to the eye, CAT and DMSO completely inhibited the occurrence of retinal degeneration and IM and PD tended to decrease its incidence, whereas DM, AA, PY, and CM showed no or an exacerbating effect. These results suggest that reactive oxygen species contribute to the initiation of auricular inflammation and retinal degeneration and that cyclooxygenase products are also involved in the initiation and later progression of auricular inflammation. They also show that histamine and 5-lipoxygenase products are not involved in either phototoxic lesion.
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PMID:Effect of antioxidants, anti-inflammatory drugs, and histamine antagonists on sparfloxacin-induced phototoxicity in mice. 899 49

We have previously demonstrated that each region of the ultraviolet (UV) spectrum (UVA, UVB, and UVC) induces the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in purified calf thymus DNA and HeLa cells in a fluence-dependent manner. In the present study, we further characterize the possible reactive oxygen species (ROS) that are involved in the induction of 8-oxodGuo by UV radiation. Sodium azide, a singlet oxygen (1O2) scavenger though its quenching effect on HO. was also reported, inhibited 8-oxodGuo production in calf thymus DNA exposed to UVA, UVB, or UVC in a concentration-dependent fashion with maximal quenching effect of over 90% at a concentration of 10 mM. Catalase, at a concentration of 50 U/ml, reduced the yields of UVA- and UVB-induced 8-oxodGuo formation by approximately 50%, but had little effect on UVC-induced 8-oxodGuo production. In contrast, 50 U/ml of superoxide dismutase (SOD) did not affect induction of 8-oxodGuo by any portion of the UV spectrum. Hydroxyl radical (HO.) scavengers mannitol and dimethylsulfoxide (DMSO) moderately reduced the levels of 8-oxodGuo induced by UVA and UVB, but not those by UVC. Instead, mannitol and DMSO enhanced the formation of 8-oxodGuo induced by UVC. These results suggest that certain types of ROS are involved in UV-induced 8-oxodGuo formation with 1O2 playing the predominant role throughout the UV spectrum. Except for UVC, other ROS such as hydrogen peroxide (H2O2) and HO. may also be involved in UVA- and UVB-induced oxidative DNA damage. Superoxide anion appears not to participate in UV-induced oxidation of guanosine in calf thymus DNA, as SOD did not display any quenching effects.
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PMID:Identification of possible reactive oxygen species involved in ultraviolet radiation-induced oxidative DNA damage. 935 40

The promutagenic base 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in DNA is known to be formed from oxygen radical attack on 2'-deoxyguanosine (dG) as a result of oxidative stress. Formation of 8-OH-dG from dG during workup is strongly dependent on temperature and transition metals and is mediated by oxygen radicals. The 8-OH-dG formation at temperatures between 0 and 140 degrees C for 1.5 h in an "ultrapure" solution followed a third-order equation. Fe2+ in the nM range mediated the formation of 8-OH-dG from dG without addition of H2O2. Fe3+, Cu+, and Cu2+ were shown to have weaker oxidative effects in comparison to Fe2+. The pH (5.0-9.0) had a very limited effect on 8-OH-dG formation. Acid phosphatase, which contains iron at its active site, caused the formation of 8-OH-dG, whereas alkaline phosphatase did not. Phenol was not found to be oxidative. Fe2+-catalyzed formation of 8-OH-dG was completely blocked by the nitroxide 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), whereas DMSO, mannitol, and DMPO had a significantly weaker protecting effect. Catalase cleaved the dG molecule and was not suitable for use. A simple, fast, and inexpensive method for 8-OH-dG workup and analysis was developed, and the background level seen in liver from 13-week-old male Sprague-Dawley rat was 0.23 +/- 0.020 8-OH-dG/10(5) dG, which is up to 200 times lower than reported values from some other methods and up to 26 times lower when compared to other reports using HPLC-EC methods. In summary, the TEMPO method reduces oxidation of dG to 8-OH-dG during workup by (1) using chemicals low in transition metals, (2) using a cold workup procedure, (3) limiting the incubation time, and (4) using the nitroxide TEMPO in all steps.
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PMID:Reduction of oxidation during the preparation of DNA and analysis of 8-hydroxy-2'-deoxyguanosine. 970 49

The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H2O2) on basal tone in aortic segments from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 6-month-old, as well as the possible mechanisms involved. Single (1 mM) or cumulative (100 nM-10 mM) concentrations of H2O2 produced a transient contraction or a concentration-dependent increase of basal tone, respectively, in segments from WKY and SHR. In both cases, the contractions were higher in intact segments from hypertensive than from normotensive rats, and increased by endothelium removal in both strains. Catalase (1000 u ml(-1), a H2O2 scavenger) abolished the contraction elicited by 1 mM H2O2 in both strains. Superoxide dismutase (SOD, 150 u ml(-1)) and dimethylsulphoxide (DMSO, 7 mM), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H2O2-induced contractions in intact segments from both strains. However, L-NG-nitroarginine methyl ester (L-NAME, 100 microM, a nitric oxide synthase inhibitor) increased the response to H2O2 in normotensive rats, although the increase was less than that produced by endothelium removal. Incubation of segments with 1 mM H2O2 for 15 min and subsequent washout reduced the contractile responses induced by 75 mM KCl in intact segments from SHR and in endothelium-denuded segments from both strains; this effect being prevented by catalase (1000 u ml(-1)). Indomethacin (10 microM, a cyclo-oxygenase inhibitor) and SQ 29,548 (10 microM, a prostaglandin H2/thromboxane A2 receptor antagonist) practically abolished the contractions elicited by H2O2 in normotensive and hypertensive rats. We conclude that: (1) the oxidant stress induced by H2O2 produces contractions mediated by generation of a product of the cyclo-oxygenase pathway, prostaglandin H2 or more probably thromboxane A2, in normotensive and hypertensive rats; (2) oxygen-derived free radicals are not involved in the effect of H2O2; (3) in normotensive rats, endothelium protects against H2O2-mediated injury to contractile machinery, determined by the impairment of KCl-induced contractions; and (4) endothelial nitric oxide has a protective role on the contractile effect induced by H2O2, that is lost in hypertension.
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PMID:Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved. 986 64

Aerial oxidation of dopamine at concentrations as low as 50 microM in the presence of ferrous ions in phosphate buffer (pH 7.4) led in the early stages (6-8 h) to the formation of the quinone of the neurotoxin 6-hydroxydopamine, 2, followed (24 h) by a complex product pattern comprising main components norepinephrine (5), 3, 4-dihydroxybenzaldehyde (4), and the neurotoxic alkaloid 6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (3). Product formation required the assistance of metal ions such as Mn(II), Zn(II), and iron, in either the ferrous or ferric form. Product yields were shown to vary linearly with iron and dopamine concentration in the early phases of the reaction (2 h). Biologically relevant antioxidants, like glutathione and ascorbate, and metal chelators, e. g., 2,2'-bipyridyl, inhibited dopamine conversion to products 2-5, but not substrate consumption, while hydroxyl radical scavengers such as DMSO and mannitol did not alter the course of the reaction. On the contrary, mannitol increased product yields, an effect seen for other monosaccharides. Catalase exhibited a significant inhibitory effect particularly on the formation of 3 and 4. By using (18)O(2), evidence was obtained for incorporation of the label into the carbonyl oxygen of 4, but not into the hydroxyl group of 5. On the basis of these and other results, a complete mechanistic picture of the oxidation is drawn involving conversion of dopamine to the corresponding o-quinone and its quinonemethide tautomer with concomitant reduction of O(2) to H(2)O(2). Nucleophilic attack by H(2)O to the quinonemethide gives rise to 5, while H(2)O(2) addition leads to benzaldehyde 4 via a beta-aminohydroperoxide intermediate. This latter reaction path also gives formaldehyde which yields the isoquinoline 3 by Pictet-Spengler condensation with dopamine. The quinone 2 results from H(2)O(2) attack at the 6-position of dopamine o-quinone in agreement with previous studies. These results provide an insight into new routes of nonenzymatic conversion of dopamine to its metabolite norepinephrine and neurotoxic species which may become operative under conditions relevant to neurodegeneration.
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PMID:New reaction pathways of dopamine under oxidative stress conditions: nonenzymatic iron-assisted conversion to norepinephrine and the neurotoxins 6-hydroxydopamine and 6, 7-dihydroxytetrahydroisoquinoline. 1056 35

We studied whether reactive oxygen species (ROS) generated by normal colonic mucosa affect 5-hydroxytryptophan (5-HTP)-evoked 5-HT formation (measured as the sum of 5-HT plus 5-hydroxyindole acetic acid (5-HIAA) accumulation) of guinea pig's isolated colonic mucosa. Catalase (3000-6000 U/ml), a hydrogen peroxide (H2O2) scavenger or diphenylene iodonium (DPI, 10-100 microM), an NADPH oxidase inhibitor, concentration-dependently caused an increase of the sum of 5-HT plus 5-HIAA accumulation in the presence of 5-HTP (10 microM), but these drugs did not significantly affect the 5-HT-metabolite in the colonic mucosa measured as the ratio of 5-HIAA/5-HT. Exogenously applied H2O2 (10-100 microM) concentration-dependently inhibited the sum of 5-HT plus 5-HIAA accumulation. In contrast, neither superoxide dismutase (SOD, 100-300 U/ml), superoxide anion scavenger, nor dimetyl sulfoxide (1-5%, DMSO), a hydroxyl radical scavenger affected the sum of 5-HT plus 5-HIAA accumulation. Moreover, mucosa ROS generation was estimated using the chemiluminescence technique. SOD (100-300 U/ml), catalase (3000-6000 U/ml) or DPI (10-100 microM), concentration-dependently reduced luminol-enhanced chemiluminescence signal from the colonic mucosa, while allopurinol (10-100 microM), a xanthine oxidase inhibitor, did not affect the chemiluminescence signal. These results suggest that ROS is formed through an NADPH oxidase system in the guinea pig colonic mucosa, where it exerts a modulatory effect on mucosal 5-HT formation upon addition of 5-HTP. Thus, ROS formation from normal colonic mucosa could be considered to contribute to the control of 5-HT production in mucosa enterochromaffin cells.
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PMID:Modification of 5-hydroxytryptophan-evoked 5-hydroxytryptamine formation of guinea pig colonic mucosa by reactive oxygen species. 1185 70

Titanium dioxide (TiO2) is a potential photosensitizer for photodynamic therapy. In this study, the mechanism of DNA damage catalyzed by photo-irradiated TiO2 was examined using [32P]-5'-end-labeled DNA fragments obtained from human genes. Photo-irradiated TiO2 (anatase and rutile) caused DNA cleavage frequently at the guanine residue in the presence of Cu(II) after E. coli formamidopyrimidine-DNA glycosylase treatment, and the thymine residue was also cleaved after piperidine treatment. Catalase, SOD and bathocuproine, a chelator of Cu(I), inhibited the DNA damage, suggesting the involvement of hydrogen peroxide, superoxide and Cu(I). The photocatalytic generation of Cu(I) from Cu(II) was decreased by the addition of SOD. These findings suggest that the inhibitory effect of SOD on DNA damage is due to the inhibition of the reduction of Cu(II) by superoxide. We also measured the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, and showed that anatase is more active than rutile. On the other hand, high concentration of anatase caused DNA damage in the absence of Cu(II). Typical free hydroxyl radical scavengers, such as ethanol, mannnitol, sodium formate and DMSO, inhibited the copper-independent DNA photodamage by anatase. In conclusion, photo-irradiated TiO2 particles catalyze the copper-mediated site-specific DNA damage via the formation of hydrogen peroxide rather than that of a free hydroxyl radical. This DNA-damaging mechanism may participate in the phototoxicity of TiO2.
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PMID:Photo-irradiated titanium dioxide catalyzes site specific DNA damage via generation of hydrogen peroxide. 1529 51


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