Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of nitric oxide (NO) and NO generating agents, on the electron transport system of mitochondria were examined in a study of the mechanism and physiological importance of NO in energy metabolism. In the presence of various substrates, uncoupled respiration was inhibited by NO in manner which was both dose- and oxygen tension-dependent. Simultaneously measuring changes in cytochrome absorption spectra and respiration showed that the site of action of NO is cytochrome oxidase. Similar inhibition was also brought about by 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC 18), an NO donor. Electron paramagnetic resonance (EPR) analysis revealed that inhibition of uncoupled respiration occurred only during the presence of NO in the reaction mixture. The inhibitory effect of NO was increased significantly by lowering the concentration of mitochondrial protein. No appreciable inhibition of respiration was observed in the presence of 3-morpholinosydnonimine (SIN-1), a peroxynitrite anion (ONOO-) generating reagent, but inhibition did occur in the presence of superoxide dismutase (SOD). These results indicate that NO reversibly interacts with mitochondria at complex IV thereby inhibiting respiration particularly under physiologically low oxygen tension and that de novo generated ONOO may have no significant effect under the present experimental conditions.
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PMID:Oxygen-dependent reversible inhibition of mitochondrial respiration by nitric oxide. 890 61

The optic nerve of the macular mouse as a model of Menkes' disease was examined by electron microscopy. Since hemizygote macular mice die at 14 or 15 days of age, they were treated with 50 micrograms CuCl2 per 0.1 ml distilled water at 7 days of age. The optic nerves of 1-month-old hemizygote macular mice treated with copper showed hypomyelination and unmyelinated axons, while 1-month-old heterozygote macular mice had focal demyelination of axons. The number of myelinated axons in treated hemizygotes and heterozygotes was statistically significantly lower than that in the control littermates. Oligodendrocytes form myelin sheaths. Since oligodendrocytes of the hemizygote macular mice may have lower activities of cuproenzymes, such as cytochrome oxidase and superoxide dismutase, hypomyelination is assumed to be caused by the dysfunction of oligodendrocyte.
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PMID:Electron microscopic study of optic nerves of macular mice. 898 67

The etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase-corrected complex II-III activity was markedly reduced in both HD caudate (-29%) and putamen (-67%), and complex IV activity was reduced in HD putamen (-62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8-hydroxydeoxyguanosine (OH8dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD.
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PMID:Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. 915 27

We took advantage of the Drosophila melanogaster's extraordinary resistance to anoxia to study the molecular mechanisms underlying this phenomenon. We analyzed mRNA expression of heat shock proteins (HSP) (HSP26 and HSP70), ubiquitins (UB) (UB3 and UB4), cytochrome oxidase I (COXI) and superoxide dismutase (SOD) using slot blot analysis. The expression of HSP genes, especially HSP70, was remarkably up-regulated (up to a thousand-fold) while those of UB4 and COXI were down-regulated (10-60%) in response to the anoxic stress. The expression of UB3 gene was up-regulated by 1.5x and the expression of SOD gene was not significantly affected. In response to heat shock stress, the expression of HSP genes increased by up to several thousand-fold, the expression of UB genes increased modestly (23-91%) but the expression of SOD and COXI genes was reduced by 25%. Furthermore, the expression patterns of HSP genes under anoxia and heat shock were clearly different. The expression of HSP genes peaked by 15 min into anoxia and then declined but stayed above baseline. In contrast, their expression increased as a function of time during heat exposure. From these results, we conclude that: (1) different forms of stress regulates gene expression in different ways; (2) anoxia differentially regulates gene expression; and (3) the up-regulation of HSP70 and down-regulation of UB4 by anoxia are consistent with the idea that Drosophila melanogaster resist anoxia, at least in part, by protecting proteins against degradation.
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PMID:Anoxia regulates gene expression in the central nervous system of Drosophila melanogaster. 919 Nov 10

Human blood mononuclear cells exposed to UVB radiation develop increased antioxidant enzyme activities. Catalase (5.50 +/- 0.65 pmol (mg protein)-1), CuZn-superoxide dismutase (16.7 +/- 2.1 pmol (mg protein)-1), Mn-superoxide dismutase (11.3 +/- 1.7 pmol (mg protein)-1), Se-dependent glutathione peroxidase (13.2 +/- 1.5 mU (mg protein)-1) and Se-independent glutathione peroxidase (3.30 +/- 0.52 mU (mg protein)-1) activities increase by 1.3-1.5-fold from the control activities after exposure to 0.3 W m-2 of 280-315 nm light for 15 min and a 3 h dark incubation period. DT-diaphorase activity (2.86 +/- 0.21 mumol DCPIP min-1 (mg protein)-1) increases threefold from the indicated control values. In contrast, cytochrome oxidase (0.36 +/- 0.04 min-1 (k') (mg protein)-1) and succinate dehydrogenase (3.06 +/- 0.25 mumol DCPIP min-1 (mg protein)-1) activities remain unchanged during the same irradiation and incubation period. The treatment of cells with cycloheximide prevents the response triggered by UVB exposure. These findings suggest that an inducible antioxidant defence mechanism operates on photo-oxidative stress and that both superoxide dismutase and DT-diaphorase may display a concerted antioxidant role.
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PMID:Antioxidant adaptive response in human blood mononuclear cells exposed to UVB. 920 76

Using immunocytochemistry we have analyzed 8 pituitary oncocytomas, 14 null cell adenomas, and 2 oncocytomas of the parotid gland (Warthin's tumor). The proportions of adenoma cells that are positive for mitochondrial protein (MP), cytochrome oxidase (COX), and manganese-superoxide dismutase (Mn-SOD) were significantly higher in pituitary oncocytomas than in null cell adenomas (MP P < 0.001, COX P < 0.001, Mn-SOD P < 0.05). In pituitary oncocytomas, MP-positive cells were distributed unevenly but in clusters or in islets admixed with some MP-negative cells, and corresponded to COX-positive cells. In contrast, almost all of the oxyphilic epithelial cells of Warthin's tumor were positive for MP, COX, and Mn-SOD. On the other hand, both pituitary tumors displayed similar findings with regard to the proportion of adenoma cells immunoreactive for copper/zinc-SOD and adenohypophysial hormones, the Ki-67 (MIB-1) proliferating cell index, and the mean number of argyrophilic nucleolar organizer regions. It was confirmed that immunocytochemical identification of MP and COX is useful for distinguishing pituitary oncocytomas from null cell adenomas. Although it remains to be determined whether oncocytomas originate from oncocytic changes of tumor cells or from neoplastic transformation of oncocytic cells, it appears that tumorigenesis of pituitary oncocytomas differs from that of Warthin's tumor.
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PMID:Immunocytochemical study of pituitary oncocytic adenomas. 922 29

When hepatocytes are incubated with the chelator diamsar, two pools can be identified, which we have termed extractable and nonextractable. On entering the hepatocyte, 67Cu first associates with the extractable pool and, after approximately 2 h, moves to the nonextractable pool. Both pools demonstrate saturation and are filled as a function of Cu concentration and incubation time. Using the Michaelis-Menten equation, we have estimated the size of the pools after incubation with 67Cu for 30 min and 4 h. During this period the extractable pool decreases in size from 200 +/- 27 to 116 +/- 5 pmol/microgram DNA, whereas the nonextractable pool increases from 28 +/- 9 to 77 +/- 11 pmol/microgram DNA. Movement of Cu from the nonextractable pool to the extractable pool is slow and incomplete. Using [3H]diamsar, we demonstrate that uptake of the chelator is not rate limiting and probably does not occur by pinocytosis. Incubation with diamsar does not affect the activity of superoxide dismutase or cytochrome-c oxidase, although it does prevent the incorporation of 67Cu into ceruloplasmin. Incubation with zinc, which induces metallothionein, results in an increase in 67Cu associated with the nonextractable pool, suggesting that 67Cu-metallothionein constitutes at least part of the nonextractable pool.
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PMID:Characterization of intracellular copper pools in rat hepatocytes using the chelator diamsar. 922 75

Mitochondria generate reactive oxygen species (ROS) as byproducts of molecular oxygen consumption in the electron transport chain. Most cellular oxygen is consumed in the cytochrome-c oxidase complex of the respiratory chain, which does not generate reactive species. The ubiquinone pool of complex III of respiration is the major site within the respiratory chain that generates superoxide anion as a result of a single electron transfer to molecular oxygen. Superoxide anion and hydrogen peroxide, derived from the former by superoxide dismutase, are precursor of hydroxyl radical through the participation of transition metals. Glutathione (GSH) in mitochondria is the only defense available to metabolize hydrogen peroxide. A small fraction of the total cellular GSH pool is sequestered in mitochondria by the action of a carrier that transports GSH from the cytosol to the mitochondrial matrix. Mitochondria are not only one of the main cellular sources of ROS, they also are a key target of ROS. Mitochondria are subcellular targets of cytokines, especially tumor necrosis factor (TNF); depletion of GSH in this organelle renders the cell more susceptible to oxidative stress originating in mitochondria. Ceramide generated during TNF signaling leads to increased production of ROS in mitochondria. Chronic ethanol-fed hepatocytes are selectively depleted of GSH in mitochondria due to a defective operation of the carrier responsible for transport of GSH from the cytosol into the mitochondrial matrix. Under these conditions, limitation of the mitochondrial GSH pool represents a critical contributory factor that sensitizes alcoholic hepatocytes to the prooxidant effects of cytokines and prooxidants generated by oxidative metabolism of ethanol. S-adenosyl-L-methionine prevents development of the ethanol-induced defect. The mitochondrial GSH carrier has been functionally expressed in Xenopus laevis oocytes microinjected with mRNA from rat liver. This critical carrier displays functional characteristics distinct from other plasma membrane GSH carriers, such as its ATP dependency, inhibitor specificity, and the size class of mRNA that encode the corresponding carrier, suggesting that the mitochondrial carrier of GSH is a gene product distinct from the plasma membrane transporters.
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PMID:GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. 925 4

The cuproenzymes lysyl oxidase, cytochrome-c oxidase, and superoxide dismutase are key factors in understanding the cardiac hypertrophy and cardiomyopathy associated with dietary copper restriction. The role of copper in cardiac lipid and energy metabolism as a consequence of changes in some of these enzyme activities in comparison with what is known about normal cardiac substrate utilization is discussed here. While the decrease in the nuclear encoded subunits of cytochrome-c oxidase in hearts from copper-deficient rats is known, new evidence suggests that other factors, such as ATP synthase metabolism may be exerting an influence upon this observation. While this review focuses on newer knowledge about energy and fatty acid metabolism in copper deficiency, the extracellular matrix is considered as well. This complex interplay of extracellular and cellular events in copper restriction is outlined as a model for further studies of this unique model of concentric hypertrophy.
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PMID:Newer findings on a unified perspective of copper restriction and cardiomyopathy. 927 Jul 15

Male Holtzman rats were offered a semipurified low-copper (Cu) diet (0.36 mg Cu/kg) for 5-6 weeks to further characterize cardiac hypertrophy, which accompanies Cu deficiency. Cu-adequate (controls) were given supplemental Cu (20 micrograms/ml) in their drinking water, and Cu-deficient rats were given deionized water. Cu-deficient rats had lower plasma ceruloplasmin activity, lower hemoglobin levels, higher heart weights, and similar body weights compared with Cu-adequate rats. The relative degree of hypertrophy in the right ventricle of Cu-deficient rats was significantly higher (2.3-fold) than that in the left ventricle and atria (both were 1.9-fold higher than the values in Cu-adequate rats). Edema was not detected. Ventricles and atria of Cu-deficient rats had markedly lower Cu and no significant differences in iron concentrations compared with Cu-adequate rats. Heart protein concentrations were not altered consistently by Cu deficiency. Enzyme activities of the cuproenzymes cytochrome-c oxidase (CCO), copper, zinc-superoxide dismutase (SOD), dopamine beta-monooxygenase (DBM), peptidylglycine alpha-amidating monooxygenase (PAM), and the selenoenzyme glutathione peroxidase (GPX) were measured in the atria and ventricles. Cu deficiency resulted in lower specific activities of all cuproenzymes, with the exception of ventricular PAM. GPX was not altered by chamber region or diet. Specific activity of PAM was 200-fold higher in atria than in ventricles in control rats. Catecholamine analyses by HPLC confirmed that, like ventricular tissue, atria of Cu-deficient rats had lower noreplnephrine and higher dopamine concentrations, consistent with lower DBM activity. Another experiment detected no differences between the two dietary groups in mean arterial blood pressure, heart rates, or responses after challenge with anglotensin II, phenylepherine, or acetylocholine in cannulated rats. In this Cu-deficient rat model, all chambers of the heart exhibit similar and marked hypertrophy. Biochemical alterations following dietary Cu deficiency were also similar in atria and ventricles. The hypertrophic response appears different from the response to simple pressure or volume overload.
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PMID:Atria and ventricles of copper-deficient rats exhibit similar hypertrophy and similar altered biochemical characteristics. 927 Jul 21


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