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)

F1F0 ATP-synthase (complex V) deficiencies in Alzheimer's disease are reported. Tissue specimens from the hippocampus of brains from patients with Alzheimer's disease were screened by blue native electrophoresis for alterations of the proteins of oxidative phosphorylation. Ubiquinol:cytochrome-c reductase (complex III) and cytochrome-c oxidase (complex IV) were found to be present at almost normal concentrations, however, complex V was substantially reduced in most cases studied. The specific reduction of complex V and the absence of electrophoretically detectable degradation products do not exclude a secondary defect of complex V, but should stimulate the search for genetic defects related to protein subunits of complex V.
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PMID:Human diseases with defects in oxidative phosphorylation. 2. F1F0 ATP-synthase defects in Alzheimer disease revealed by blue native polyacrylamide gel electrophoresis. 786 55

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
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PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64

The cytochrome bc complex which is encoded by the fixNOPQ operon in Bradyrhizobium japonicum, is the most distant member of the haem-copper cytochrome oxidase family. We have found that its major subunit, FixN, is homologous to the NorB subunit of nitric oxide reductase in a purple bacterium. A second evolutionary link between cytochrome oxidases and denitrification enzymes is the presence of a similar binuclear copper site in cytochrome aa3 (the mitochondrial oxidase) and nitrous oxide reductase. This centre was probably acquired by a primitive FixN-type oxidase, leading to the evolution of the mitochondrial-type oxidase. These links suggest that the oxygen-reducing respiratory chain developed from the anaerobic, denitrifying respiratory system.
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PMID:Cytochrome oxidase evolved by tinkering with denitrification enzymes. 813 5

The structural gene for the respiratory nitrous-oxide reductase from Paracoccus denitrificans has been cloned using a probe derived from the structural gene, nosZ, for this enzyme from Pseudomonas stutzeri. The cloned gene could be expressed surprisingly well (presumably yielding an apo-protein) using an expression vector in Escherichia coli. Sequencing the nosZ gene from P. denitrificans has shown that the periplasmic nitrous-oxide reductase of this organism is highly similar in sequence to previously derived primary sequences for the enzyme from three other organisms. As with the other reductases, an unusually long signal sequence is deduced and a common motif of GXXRRXXLG near the beginning of this sequence is present. The results of N-terminal sequencing of the mature nitrous-oxide reductase from the closely related organism Thiosphaera pantotropha indicate that processing of the P. denitrificans precursor occurs between amino acids at positions 57 and 58. The predicted signal peptide is therefore of the same length and of similar overall structure to that previously described for the P. denitrificans methylamine dehydrogenase small subunit (MauA). The P. denitrificans sequence for the mature nitrous-oxide reductase reduces from 14 to 11 and 6 to 4, respectively, the number of conserved histidine and methionine residues compared to previous sequences. Three cysteine and four tryptophan residues, previously identified as conserved amongst nitrous-oxide reductases, are found in the Paracoccus enzyme. A comparison of the sequence of the C-terminal region of the nitrous-oxide-reductase sequence with that for the CuA region of subunit II of the cytochrome aa3 from P. denitrificans reveals considerable sequence similarities. Upstream of the structural gene for nosZ are sequences TTGAAGCTTAACCAG (centred at position -21 with respect to the start codon) and CCCGGTGGTCATCAAG (centred at position -126). Although both could be FNR (ANR) boxes, the latter is far more probable to have this role because only it is likely to be upstream of a promoter site. This is the first indication at the DNA sequence level for the existence of this regulatory system in P. denitrificans. Analysis of the flanking DNA sequences revealed reading frames upstream and downstream of the nosZ gene showing similarity to the nosR and nosD genes, respectively, of Pseudomonas species. An S30 in vitro transcription/translation system was developed for P. denitrificans which permitted the expression of the cloned gene for nitrous-oxide reductase and which will be of general value in other studies of this organism.
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PMID:Sequence and expression of the gene encoding the respiratory nitrous-oxide reductase from Paracoccus denitrificans. New and conserved structural and regulatory motifs. 824 76

Nitric oxide (.NO) released by S-nitrosoglutathione (GSNO) inhibited enzymatic activities of rat heart mitochondrial membranes. Cytochrome oxidase activity was inhibited to one-half at an effective .NO concentration of 0.1 microM, while succinate- and NADH-cytochrome-c reductase activities were half-maximally inhibited at 0.3 microM .NO. Submitochondrial particles treated with .NO (either from GSNO or from a pure solution) showed increased O(-)(2) and H202 production when supplemented with succinate alone, at rates that were comparable to those of control particles with added succinate and antimycin. Rat heart mitochondria treated with .NO also showed increased H2O2 production. Cytochrome spectra and decreased enzymatic activities in the presence of .NO are consistent with a multiple inhibition of mitochondrial electron transfer at cytochrome oxidase and at the ubiquinone-cytochrome b region of the respiratory chain, the latter leading to the increased O2- production. Electrochemical detection showed that the buildup of a .NO concentration from GSNO was interrupted by submitochondrial particles supplemented with succinate and antimycin and was restored by addition of superoxide dismutase. The inhibitory effect of .NO on cytochrome oxidase was also prevented under the same conditions. Apparently, mitochondrial O2- reacts with .NO to form peroxynitrate and, by removing .NO, reactivates the previously inhibited cytochrome oxidase. It is suggested that, at physiological concentrations of .NO, inhibition of electron transfer, .NO-induced O2- production, and ONOO- formation participate in the regulatory control of mitochondrial oxygen uptake.
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PMID:Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. 863 42

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36

The neuron cell bodies and microvessels in sections of the nodose (vagal sensory) ganglion (NG) of Wistar rats of 4- and 24-months of age have been examined morphometrically and by quantitative enzyme histochemistry. The range of neuronal somata areas was similar at the two ages and distributed unimodally, ranging approximately from 200-1500 microns 2 with the largest somata occurring in the older age group. The range of microvessel diameters was also comparable but the largest microvessels were seen in the older animals. The histological arrangement of the ganglion permitted analyses to be made of 'neuronal' and 'axonal' areas independently. The number of microvessels per unit area was less in regions of the ganglion occupied by axons at both ages. Random transects indicated that the percentage area occupied by neuron somata decreases and that of axons increases with age. Overall, however, the results suggest that the histological organization, the size of vagal sensory neurons, the ganglionic microvessels, and the relationship between them, does not change greatly in Wistar rats of up to 2 years of age. Ultrastructural features of the aged sensory neurons included the presence of secondary lysosomes, disrupted rough endoplasmic reticulum, swollen Golgi cisternae, and the presence of much filamentous material in the perikaryon similar to that seen in chromatolytic neurons. However, analysis of electron micrographs did not reveal significant changes in the numbers of mitochondria or Golgi bodies. There was an overall increased thickness in the microvascular wall in the older animals with the endothelium and pericyte covering being significantly increased, but the thickness of the basal lamina was unchanged. The activities of neuronal NADH tetrazolium reductase, succinate dehydrogenase and cytochrome oxidase were all increased with age. The results suggest that vagal sensory neurons are not greatly affected by age in the rat.
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PMID:Neurons and microvessels of the nodose (vagal sensory) ganglion in young adult and aged rats: morphometric and enzyme histochemical studies. 885 85

The vagus nerve trunk, sampled at a mid-cervical level, has been analysed quantitatively by light and electron microscopy principally with respect to the numbers and sizes of the myelinated and unmyelinated axon populations in Wistar rats of 4, 24 and 30 months. No significant differences in total myelinated axon numbers were seen over the age range in counts made on light microscope montages of the entire cross-section of the nerve. The overall histological organisation and appearance of the nerve trunk did not change with age but age-associated alterations in the ultrastructure of some myelinated fibres and their Schwann cells was seen. Unmyelinated axons and their associated Schwann cells rarely showed age-associated changes. The numbers of myelinated and unmyelinated axons per mm2 determined from electron micrographs were, however, slightly decreased but the ratio of myelinated to unmyelinated axons was approximately 1:4 at all ages. Measurements of myelinated fibres showed a small but significant increase in size between young and old animals. There was an increase in the thickness of the myelin sheath, a decrease in myelinated axon diameter and in the the g ratio. The diameter of unmyelinated axons decreased with age and the number of unmyelinated axons per Schwann cell unit increased. The numbers, diameters and thickness of the walls of the vagal microvessels remained unchanged. Quantitation by microdensitometry of the activity of NADH tetrazolium reductase and succinate dehydrogenase in longitudinal sections of the vagus indicated an increase in the activity of these two metabolic markers whilst an increase in the activity of cytochrome oxidase indicated that neuronal activity in the vagus was unimpaired in old age. It is concluded that the structure of the rat vagus nerve, and in particular of its predominantly unmyelinated axon population, is not significantly affected in old age.
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PMID:Preservation of the cervical vagus nerve in aged rats: morphometric and enzyme histochemical evidence. 888 1

In this study we describe a novel experimental approach to quantify the relative susceptibility of (membrane-associated, contractile and mitochondrial) proteins in normal human muscle tissue sections to oxidative damage by the reactive oxygen species (ROS), hydroxyl (OH.) or superoxide (O2.-) radicals. The latter species were generated under controlled experimental conditions in vitro using a 60Co gamma radiation source, with subsequent analysis of damage to target proteins (dystrophin, beta-dystroglycan, beta-spectrin, fast and slow myosin heavy chain, NADH tetrazolium reductase, succinate dehydrogenase and cytochrome oxidase) via standard histochemistry, immunocytochemistry and electron microscopy of muscle tissue sections. In general terms, each of the proteins listed above was more susceptible to oxidative damage by OH., compared to O2.-. Different proteins (differing in structure, function or intracellular localisation) showed different susceptibility to oxidative damage, with certain mitochondrial proteins (succinate dehydrogenase, cytochrome oxidase) showing particular susceptibility. In addition, the use of monoclonal antibodies to four different regions of dystrophin showed the latter to contain both resistant and susceptible regions to ROS induced oxidative damage. At the ultrastructural level of subcellular organelle damage, mitochondria were identified as being particularly susceptible to ROS induced oxidative damage. We therefore speculate that oxidative damage to mitochondria and/or mitochondrial proteins may represent the principal initial route of free radical-induced damage within skeletal muscle tissue.
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PMID:Differential susceptibility of human skeletal muscle proteins to free radical induced oxidative damage: a histochemical, immunocytochemical and electron microscopical study in vitro. 889 Oct 64

Gene expression has been studied in post-mortem frontal cortex samples from patients who had suffered from schizophrenia and depressive illness. mRNA was extracted and characterised by translation and separation of the products by 2D gel electrophoresis. Post-mortem artefacts and the agonal experience did not affect the size distribution or amount of specific translation products. Four expression products were specifically reduced in samples from schizophrenics compared with normals. The expression of six products was altered in affective disorder, one in common with schizophrenia, two the same as in schizophrenia but increased. cDNA libraries were produced from the mRNA samples and 5 clones present at abnormal levels in schizophrenia identified by differential screening, isolated and sequenced. All the sequences encode mitochondrial transcripts; four encode mitochondrial rRNA and one the amino acid sequence of cytochrome oxidase sub-unit II. Increased cytochrome oxidase transcripts were found in a further set of mRNA extracts from schizophrenic patients including two who had not received neuroleptic medication. The effects of neuroleptic administration as exemplified by alpha-flupenthixol compared with the ineffective beta-flupenthixol were studied in experimental animals. It was found that 13 out of 28 clones whose levels were altered were mitochondrial in origin including rRNA, COX I & II and the NADH-Q reductase. Those encoding respiratory enzymes were at abnormally low levels as a result of alpha-flupenthixol administration. Measurements of the enzymic activity of cytochrome c oxidase in post-mortem frontal cortex of schizophrenics did not indicate any differences in overall activity but there was a decreased sensitivity to azide that was abolished by neuroleptics. Studies on NADH-cytochrome c reductase showed that schizophrenics whether medicated or not had a reduced rotenone sensitive activity that was compensated for by increased rotenone insensitive activity. We conclude that changes in mitochondrial gene expression are involved in schizophrenia and probably other functional psychoses.
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PMID:Mitochondrial involvement in schizophrenia and other functional psychoses. 889 62


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