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

Copper thiosemicarbazones cause considerable oxidative stress. This effect may be related to their cytotoxicity. In the present work, the chemical and cellular properties of a new ligand, pyridoxal thiosemicarbazone (H2T), and its copper(II) chelate (CuT) are assessed. CuT is toxic to cultured Ehrlich ascites tumor cells, producing nearly complete cell kill at drug/cell ratios of 2.5-4 nmol/10(5) cells in a monolayer culture over a 48-h treatment period. This concentration is at least 1 order of magnitude lower than those required for a similar degree of cytotoxicity by H2T or CuCl2. The following observations support the view that activated oxygen species are generated by interaction of CuT with Ehrlich cells: (1) Room-temperature electron spin resonance spectroscopy and atomic absorption measurements show rapid cellular uptake and CuT-thiol adduct formation. (2) Cellular thiol content is reduced. (3) High levels of DNA strand scission result from 1-h treatments of cells by concentrations of CuT that cause growth inhibition and toxicity. (4) The extent of strand scission can be increased by addition of superoxide dismutase and decreased by catalase or DMSO in the treatment medium. Catalase and DMSO do not inhibit the toxic effect of CuT. This suggests that DNA damage is not responsible for inhibition of cell proliferation by CuT.
 ...
PMID:Oxidative stress induced by a copper-thiosemicarbazone complex. 217 40

Explanted hepatic granulomas, eosinophils obtained from the peritoneal cavity of schistosome-infected mice, schistosome egg granuloma macrophages, alveolar macrophages, and activated peritoneal macrophages obtained from Listeria-infected mice were miracidicidal when cultured at 21% oxygen. This activity was markedly attenuated at physiologic oxygen concentrations (1-15%). Catalase and superoxide dismutase blocked the miracidicidal activity of inflammatory cells but did not prevent granuloma-mediated egg killing. However, the biomimetic superoxide dismutase, copper (II) [diisopropyl salicylate]2, inhibited granuloma-mediated egg killing in a dose-dependent, apparently nontoxic manner. Thioglycollate-elicited macrophages did not kill schistosome egg miracidia even when cultured in 21% oxygen, unless pretreated with lipopolysaccharide. Isolated schistosome eggs initiated an oxidative burst in macrophages, as measured by superoxide anion production. This burst was suppressed at reduced oxygen concentrations. Thus schistosome egg miracidia can be killed nonspecifically by macrophages through the release of cytotoxic reactive oxygen intermediates triggered by the egg. This activity is not supported by the oxygen concentrations found in most tissues, with the possible exception of the lung. Schistosoma mansoni eggs, injected intraveneously and lodged in the pulmonary vasculature of mice, were killed rapidly, with a half life of 3.5 days. Eggs, injected into the mesenteric veins and lodged in the liver, remained fully viable for several weeks. The data suggest that the high oxygen tension of the lung allows for the increased production of reactive oxygen intermediates (ROI) by local inflammatory cells, which in turn increases their miracidicidal efficiency. Conversely, the relatively hypoxic environment of the liver decreases ROI production by local inflammatory cells and decreases their miracidicidal efficiency.
 ...
PMID:Physiologic oxygen tensions limit oxidant-mediated killing of schistosome eggs by inflammatory cells and isolated granulomas. 231 8

The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 micrograms protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 micrograms protein/ml, but with a similar maximal contraction at 100 micrograms protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine. Thus, oxidized low density lipoproteins caused endothelium-dependent coronary artery contractions which are mediated by a hydroperoxide. Contractions to native low density lipoproteins are due to their oxidation in the organ chamber by the superoxide anion radical. Oxidized, but not native, low density lipoproteins impair normal endothelial cell vasodilator function in vitro. Oxidized low density lipoproteins, important in the pathogenesis of atherosclerosis, may directly contribute to the increased risk of vasospasm seen in hypercholesterolemia and atherosclerosis.
 ...
PMID:Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. 236 28

The activities of superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase were measured in isolated brain capillaries, choroid plexus, cerebrum, and cerebellum from rats of 2, 6, 12, and 24 months. The contents of copper, zinc, and manganese were determined in capillaries, cerebrum, and cerebellum, and the profile of fatty acids was studied in brain capillaries. In brain capillaries, the activities of glutathione peroxidase and glutathione reductase did not change with age. The activities of the two enzymes increased in cerebrum and cerebellum. In choroid plexus, glutathione peroxidase activity increased, but glutathione reductase activity remained unchanged. Catalase activity in brain capillaries declined, whereas in choroid plexus, cerebrum, and cerebellum, it did not change. The activities of the three enzymes were significantly higher in brain capillaries and choroid plexus than in cerebrum and cerebellum. SOD activity increased in the four tissues. Copper content in the capillaries increased initially and then levelled off, whereas it continued to increase in cerebrum and cerebellum. Zinc increased in brain capillaries, but did not vary in cerebrum and cerebellum. Manganese content remained constant in all tissues studied. The percent of saturated fatty acids in brain capillaries did not change with age, whereas those of mono- and polyunsaturated fatty acids increased and decreased, respectively. The possibility that a deficiency of enzymes protective against free radicals causes blood-brain barrier and blood-cerebrospinal fluid barrier degeneration is ruled out.
 ...
PMID:Antioxidant enzymes and related trace elements in aging brain capillaries and choroid plexus. 276 Jun 21

The mechanisms underlying drug-induced neutropenia are poorly characterized. We have examined the mechanism of suppression of granulocytopoiesis by captopril and penicillamine using human and canine bone marrow cells in an in vitro culture system. Addition of captopril caused no significant change in granulocyte-macrophage colony formation at concentrations up to 30 micrograms/ml. In the presence of CuSO4 (1-3 micrograms/ml), however, captopril caused significant inhibition of colony growth (p less than 0.05). Penicillamine, another agent associated with neutropenia and, like captopril, having a reactive thiol group, also inhibited colony formation in the presence of copper. Chemical congeners of captopril lacking a reactive thiol group and enalaprilic acid, an alternative angiotensin-converting enzyme (ACE) inhibitor, failed to show inhibition, suggesting that the thiol group and not ACE inhibition was responsible. Analysis of day-7 colonies (98% neutrophilic) and day-21 colonies (37% neutrophilic, 30% macrophagic, 27% eosinophilic, and 6% mixed) showed that neutrophil-containing colonies, but not nonneutrophilic colonies were inhibited by the addition of captopril plus copper. Catalase totally reversed the inhibition of colony formation caused by these agents. Direct measurement of oxygen consumption in the presence of captopril showed marked enhancement with the addition of CuSO4 and a 48% reduction in the presence of added catalase. These data indicate that drugs with a reactive thiol group can interact with copper to generate H2O2, which can be toxic to neutrophilic progenitor cells. We postulate that this may be an important mechanism for drug-associated neutropenia and a general mechanism for drug-induced marrow cell injury.
 ...
PMID:Suppression of in vitro granulocytopoiesis by captopril and penicillamine. 284 Nov 47

The activity of acetyl-CoA hydrolase (dimeric form) purified from the supernatant fraction of rat liver was shown to have a half-life (t1/2) of 3 min at 0 degree C, but to stable at 37 degrees C (t1/2 = 34 h) [Isohashi, F., Nakanishi, Y. & Sakamoto, Y. (1983) Biochemistry 22, 584-590]. Incubation of the purified enzyme with L-ascorbic acid (AsA) at 37 degrees C resulted in inactivation of the enzyme (t1/2 = 90 min at 2 mM AsA). The extent of inactivation was greatly enhanced by addition of transition metal ions (Cu2+, Fe2+, and Fe3+). Thiol reducing agents, such as reduced glutathione and DL-dithiothreitol, protected the hydrolase from inactivation by AsA. However, these materials did not restore the catalytic activity of the enzyme inactivated by AsA. When AsA solution containing Cu2+ was preincubated under aerobic conditions at 37 degrees C for various times in the absence of enzyme, and then aliquots were incubated with the enzyme solution for 20 min, remaining activity was found to decrease with increase in the preincubation time, reaching a minimum at 60 min. However, further preincubation reduced the potential for inactivation. Catalase, a hydrogen peroxide (H2O2) scavenger, almost completely prevented inactivation of the enzyme by AsA plus Cu2+. Superoxide dismutase and tiron, which are both superoxide (O2-) scavengers, also prevented inactivation of the enzyme. A high concentration of mannitol, a hydroxyl radical (OH) scavenger, partially protected the enzyme from inactivation. These results suggest that inactivation of the enzyme by AsA in the presence of Cu2+ was due to the effect of active oxygen species (H2O2, O2-, OH) that are known to be autoxidation products of AsA. Valeryl-CoA, a competitive inhibitor of acetyl-CoA hydrolase, greatly protected the enzyme from inactivation by AsA plus Cu2+, but ATP and ADP, which are both effectors of this enzyme, had only slight protective effects. These results suggest that inactivation of this enzyme by addition of AsA plus Cu2+ was mainly due to attack on its active site.
 ...
PMID:Oxidative inactivation of an extramitochondrial acetyl-CoA hydrolase by autoxidation of L-ascorbic acid. 286 35

Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4-benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron-spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed.
 ...
PMID:Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite. 290 43

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a stimulator of chemiluminescence (CL) in SENCAR mouse epidermal cells. The CL response is TPA dose dependent (8 to 800 nM) as well as proportional to the number of cells used. Treatment with 166 nM TPA results in a CL response that peaks by 15 min although a strong response persists for over 30 min. The CL response can be inhibited by superoxide dismutase and the superoxide dismutase mimetic copper(II) (3,4 diisopropylsalicylic acid)2, suggesting that the CL response may be due to or mediated by superoxide anions. Catalase, which is specific for H2O2, and mannitol, which is a scavenger for hydroxyl radicals, had negligible inhibitory effects. The CL response is also inhibited by retinoic acid and the analogue ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8- nonatetraenoate. A series of phorbol esters with different promoting abilities produced corresponding CL responses. The second stage tumor promoter mezerein is as effective as TPA in stimulating CL. Inhibitors of various parts of the arachidonic acid cascade were found to affect the TPA-induced CL response in a manner that corresponds to their effects in vivo tumor promotion experiments: agents which are predominantly lipoxygenase inhibitors, i.e., nordihydroguaiaretic acid, benoxaprofen, or agents which are effective against both lipoxygenase or cyclooxygenase, i.e., 5,8,11,14-eicosatetraynoic acid and phenidone, are effective in diminishing the CL response. Cyclooxygenase inhibitors, i.e., indomethacin and flurbiprofen, have no or a slight enhancing effect at low doses. These data suggest that at least a major part of the TPA-induced CL response is due to the metabolism of arachidonic acid, most probably by the lipoxygenase(s). This CL assay may provide a useful system for studying the involvement of oxidants in tumor promotion.
 ...
PMID:Suppression of tumor promoter-induced chemiluminescence in mouse epidermal cells by several inhibitors of arachidonic acid metabolism. 298 61

Multiple lines of evidence show that oxidation products of ascorbic acid (vitamin C) are capable of inducing a variety of genetic alterations in microbial and mammalian cells. We have studied the inactivation kinetics in repair proficient and deficient Escherichia coli K12 cells treated with oxidized solutions of ascorbic acid, in the presence of catalytic amounts of copper. Our results suggest that the repair pathways controlled by the recA and uvrA gene products (the latter in a recA strain) contribute to cell survival. However, the lack of beta-galactosidase induction, in the SOS chromotest, implies a role for the RecA protein other than SOS induction. Catalase and thiourea suppress the toxic effects of oxidized ascorbate solutions, confirming that H2O2 and hydroxyl radicals are intermediate agents in the damaging action. Single-strand breaks were detected in DNA from treated cells.
 ...
PMID:Ascorbate-copper induced DNA lesions and repair in Escherichia coli K12 cells. 300 73

Growth of Saccharomyces cerevisiae in the presence of paraquat caused an increase the intracellular flux of superoxide radicals and in superoxide dismutase biosynthesis. The addition of copper to the growth medium also elicited an increase in superoxide dismutase levels. A cytochrome c deficient mutant strain was found to be more responsive than the wild type strain to paraquat and/or copper by increasing its copper-zinc superoxide dismutase. Catalase activity in both strains was not significantly affected by paraquat and/or copper.
 ...
PMID:Biosynthesis of superoxide dismutase in Saccharomyces cerevisiae: effects of paraquat and copper. 301 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>