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)

Antibodies to glutamate (Glu) were used to study the effects of reduced afferent input on excitatory neurons in the somatic sensory cortex of adult monkeys. In each monkey, immunocytochemical staining was compared to thionin and cytochrome oxidase (CO) staining in adjacent sections. In the cervical spinal cord, dorsal column nuclei, ventroposterior thalamus, and primary somatic sensory cortex (SI), Glu immunoreactivity (Glu-ir) was analogous to that described in normal animals; regions with reduced or absent Glu-ir were never observed and no appreciable differences were noted between the experimental and normal side. There were also no differences in CO or thionin-stained sections from the affected hemisphere. In the insuloparietal operculum, sections in the hemisphere contralateral to the nerve cut showed that most cortical fields had a normal pattern of Glu-ir (pattern a), some exhibited a reduction of Glu-ir (pattern b), and that in the central portion of the upper bank of the central sulcus, which corresponds to the general location of the hand representation of the second somatic sensory cortex (SII), Glu-ir had virtually disappeared (pattern c). Adjacent sections processed for CO or stained with thionin showed that in the regions corresponding to those characterized by pattern c, CO was slightly decreased and that glial cells had increased in number. In the regions of SII characterized by pattern c, small intensely stained glial cells displayed Glu-ir. These findings indicate that Glu-ir is regulated by afferent activity and suggest that changes in Glu levels in neurons as well as in glial cells may trigger the biochemical processes underlying the functional and structural changes occurring during a slow phase of reorganizational plasticity in the cerebral cortex of adult monkeys.
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PMID:Changes in glutamate immunoreactivity in the somatic sensory cortex of adult monkeys induced by nerve cuts. 874 39

One of the hallmarks of the primate striate cortex is the presence of cytochrome oxidase (CO)-rich puffs and CO-poor interpuffs in its supragranular layers. However, the neurochemical basis for their differences in metabolic activity and physiological properties is not well understood. The goals of the present study were to determine whether CO levels in postsynaptic neuronal compartments were correlated with the proportion of excitatory glutamate-immunoreactive (Glu-IR) synapses they received and if Glu-IR terminals and synapses in puffs differed from those in interpuffs. By combining CO histochemistry and postembedding Glu immunocytochemistry on the same ultrathin sections, the simultaneous distribution of the two markers in individual neuronal profiles was quantitatively analyzed. As a comparison, adjacent sections were identically processed for the double labeling of CO and GABA, an inhibitory neurotransmitter. In both puffs and interpuffs, most axon terminals forming asymmetric synapses (84%)--but not symmetric ones, which were GABA-IR--were intensely immunoreactive for Glu. GABA-IR neurons received mainly Glu-IR synapses on their cell bodies, and they had three times as many mitochondria darkly reactive for CO than Glu-rich neurons, which received only GABA-IR axosomatic synapses. In puffs, GABA-IR neurons received a significantly higher ratio of Glu-IR to GABA-IR axosomatic synapses and contained about twice as many darkly CO-reactive mitochondria than those in interpuffs. There were significantly more Glu-IR synapses and a higher ratio of Glu- to GABA-IR synapses in the neuropil of puffs than of interpuffs. Moreover, Glu-IR axon terminals in puffs contained approximately three times more darkly CO-reactive mitochondria than those in interpuffs, suggesting that the former may be synaptically more active. Thus, the present results are consistent with our hypothesis that the levels of oxidative metabolism in postsynaptic neurons and neuropil are positively correlated with the proportion of excitatory synapses they receive. Our findings also suggest that excitatory synaptic activity may be more prominent in puffs than in interpuffs, and that the neurochemical and synaptic differences may constitute one of the bases for physiological and functional diversities between the two regions.
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PMID:Differential glutamatergic innervation in cytochrome oxidase-rich and -poor regions of the macaque striate cortex: quantitative EM analysis of neurons and neuropil. 876 29

Site-directed mutagenesis was used to investigate the mechanism of electron and proton transfer in the ubiquinol oxidase, cytochrome bo3, from Escherichia coli. The reaction between the fully reduced form of the enzyme and dioxygen was studied using the flow--flash method. After rapid mixing of CO-bound enzyme with an O2-containing solution, CO was photodissociated, and the subsequent electron- and proton-transfer reactions were measured spectrophotometrically, the latter using a pH-indicator dye. In the wild-type, pure bo3 enzyme, without bound quinones, we observed a single kinetic phase with a rate constant of about 2.4 x 10(4) s-1, associated with formation of the ferry1 oxygen intermediate, followed by proton uptake from solution with a rate constant of about 1.2 x 10(4) s-1. Enzyme in which heme o instead of heme b was incorporated into the low-spin site displayed a slower ferry1 formation with a rate constant of about 3.6 x 10(3) s-1. Upon replacement of the acidic residue glutamate 286 in helix VI of subunit I with a nonprotonatable residue, electron transfer was slightly accelerated, and proton uptake was impaired. Mutations of other residues in the vicinity of E286 also resulted in a dramatic decrease of proton uptake, suggesting that the environment of this residue is important for efficient proton transfer. In the closely related cytochrome aa3 from P. denitrificans, the corresponding residue (E278) has been suggested to be part of a proton-transfer pathway [Iwata, S., Ostermeier, C., Ludwig, B., & Michel, H. (1995) Nature 376, 660-669]. The results are discussed in terms of a model for electron-proton coupling during dioxygen reduction.
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PMID:Kinetics of electron and proton transfer during the reaction of wild type and helix VI mutants of cytochrome bo3 with oxygen. 888 47

The legume Vicia sativa (common vetch) harbors the neurotoxic nonprotein amino acid beta-cyano-L-alanine (BCLA) and its gamma-glutamyl derivative. BCLA elicits hyperexcitability, convulsions, and rigidity in chicks and rats after oral or intraperitoneal administration, but the mechanism of its action is unknown. The effect of different concentrations of BCLA (0.075-10.0 mM) has been investigated in an organotypic tissue culture system. BCLA concentrations of 0.075 and 0.60 mM had no effect, even up to 6 hr. No changes were observed in cultures treated with 1 mM BCLA for 4 hr. BCLA (2.0-10.0 mM) induces concentration-dependent changes in the explants. The explants display neurona vacuolation, chromatin, clumping, and dense shrunken cells, a pathological response generally seen with excitotoxin. MK-801 (35 microM), which blocks the open ion channel associated with the N-methyl-D-aspartate (NMDA) class of glutamate receptors, attenuates the neurotoxic property of BCLA, while the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), provides no significant protection. Treatment of isolated mouse brain mitochondria with up to 5 mM BCLA had no inhibitory effect on the activity of NADH dehydrogenase (complex I) or cytochrome or oxidase (complex IV), a cyanide-sensitive enzyme. These results suggest that the neurotoxicity of BCLA (or derivative) is mediated directly or indirectly through NMDA receptors.
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PMID:beta-Cyano-L-alanine toxicity: evidence for the involvement of an excitotoxic mechanism. 902 49

Experiments were performed on eight subjects affected by peripheral arterial occlusive disease (PAOD) of the lower limbs. Each patient was submitted to Ecodoppler, angiography and the "Treadmill test". Two bioptic muscle of these patients. A sample was used for the spectrophotometric and spectrophotofluorimetric determinations of: glycogen, pyruvate, lactate, citrate, alpha-ketoglutarate, malate, aspartate, glutamate, AMP, ADP, ATP and creatine phosphate (CP). The other bioptic sample was used to determine the following enzyme activities: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase, aspartate aminotransferase and alanine aminotransferase. Patients showed an increase in lactate dehydrogenase, total NADH cytochrome c reductase and succinate dehydrogenase activities, a decrease in glycogen, ATP and CP concentrations. Telethermographic data showed patient muscle thermic emission quantitatively different from control group. The telethermographic test can be used as an additional diagnostic tool to determine and monitor the efficiency of a muscle undergoing metabolic failure.
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PMID:Instrumental and metabolic evaluation of patients affected by peripheral arterial occlusive disease (PAOD) following surgical revascularization surgery. 928 78

The structural genes for the NO reductase in Paracoccus halodenitrificans, norC, norB, and norQ were sequenced. The norC and norB encode the cytochrome c (NorC) and cytochrome b (NorB) subunits, respectively. The matured NorC (17,258 Da, 148 residues) has a binding motif (CXYCH) for heme c, which is axially coordinated by His65 and Met115. NorB (52,337 Da, 451 residues) has twelve putative transmembrane helices and the 19% sequence homology with the subunit I of cytochrome oxidase from Paracoccus denitrificans. Several histidine and glutamate residues were identified as the ligands for two hemes b and a non-heme iron in comparison with the sequence of cytochrome oxidase. The higher-order model structures constructed from the amino acid sequences of NorC and NorB showed the topology of the helical segments and the locations of the metal centers.
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PMID:Genomic DNA cloning of the region encoding nitric oxide reductase in Paracoccus halodenitrificans and a structure model relevant to cytochrome oxidase. 948 Aug 21

The primary visual cortex (V1) of primates is unique in that it is both the recipient of visual signals, arriving via parallel pathways (magnocellular [M], parvocellular [P], and koniocellular [K]) from the thalamus, and the source of several output streams to higher order visual areas. Within this scheme, output compartments of V1, such as the cytochrome oxidase (CO) rich blobs in cortical layer III, synthesize new output pathways appropriate for the next steps in visual analysis. Our chief aim in this study was to examine and compare the synaptic arrangements and neurochemistry of elements involving direct lateral geniculate nucleus (LGN) input from the K pathway with those involving indirect LGN input from the M and P pathways arriving from cortical layer IV. Geniculocortical K axons were labeled via iontophoretic injections of wheat germ agglutinin-horseradish peroxidase into the LGN and intracortical layer IV axons (indirect P and M pathways to the CO-blobs) were labeled by iontophoretic injections of Phaseolus vulgaris leucoagglutinin into layer IV. The neurochemical content of both pre- and postsynaptic profiles was identified by postembedding immunocytochemistry for gamma-amino butyric acid (GABA) and glutamate. Sizes of pre- and postsynaptic elements were quantified by using an image analysis system, BioQuant IV. Our chief finding is that K LGN axons and layer IV axons (indirect input from M and P pathways) exhibit different synaptic relationships to CO blob cells. Specifically, our results show that within the CO blobs: 1) all K cell axons contain glutamate, and the vast majority of layer IV axons contain glutamate with only 5% containing GABA; 2) K axons terminate mainly on dendritic spines of glutamatergic cells, while layer IV axons terminate mainly on dendritic shafts of glutamatergic cells; 3) K axons have larger boutons and contact larger postsynaptic dendrites, which suggests that they synapse closer to the cell body within the CO blobs than do layer IV axons. Taken together, these results suggest that each input pathway to the CO blobs uses a different strategy to contribute to the processing of visual information within these compartments.
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PMID:Synaptic and neurochemical characterization of parallel pathways to the cytochrome oxidase blobs of primate visual cortex. 948 23

Previously, we found that cytochrome oxidase-rich zones in the supragranular layers of the macaque striate cortex had more asymmetric, glutamate-immunoreactive synapses than the surrounding, cytochrome oxidase-poor regions. A major glutamate receptor family is N-methyl-D-aspartate, which is implicated in the stimulation of nitric oxide synthase and in the production of nitric oxide, a gaseous intra- and inter-cellular messenger. To determine if energy-generating and energy-utilizing enzymes bore any spatial relationship with neurochemicals associated with glutamatergic neurotransmission in the monkey visual cortex, serial cortical sections were processed histochemically for cytochrome oxidase and NADPH-diaphorase, and immunohistochemically for sodium/potassium-ATPase, nitric oxide synthase, and N-methyl-D-aspartate receptor subunit 1 protein, respectively. The general patterns were similar among the five neurochemicals, with layers 4C, 6 and supragranular puffs being labelled, although the intensity of labelling differed among them. Monocular impulse blockade with tetrodotoxin for two to four weeks induced a down-regulation of all five neurochemicals not only in deprived layer 4C ocular dominance columns, but also in deprived rows of puffs. Thus, the regulation of all five neurochemicals in the mature visual cortex is activity-dependent. Combined cytochrome oxidase histochemistry and nitric oxide synthase immunohistochemistry in the same sections revealed that double-labelled cells were primarily medium-sized non-pyramidals in various cortical layers. Likewise, those that were double-labelled by N-methyl-D-aspartate receptor subunit 1 immunohistochemistry and nitric oxide synthase immunogold silver staining in the same sections were of the medium-sized non-pyramidal neurons. At the ultrastructural level, combined cytochrome oxidase cytochemistry and postembedding immunogold labelling for nitric oxide synthase showed that immunogold particles for nitric oxide synthase were more heavily concentrated in cytochrome oxidase-rich type C cells. These medium-sized non-pyramidal cells were previously found to be gamma aminobutyric acid-immunoreactive and received both gamma aminobutyric acid- and glutamate-immunoreactive axosomatic synapses. Thus, our results are consistent with an enrichment of excitatory synaptic interactions in metabolically active regions of the primate visual cortex that involves glutamate-related neurochemicals, such as N-methyl-D-aspartate receptors and nitric oxide synthase. These interactions impose a higher energy demand under normal conditions and are down-regulated by retinal impulse blockade.
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PMID:Neurochemical organization of the macaque striate cortex: correlation of cytochrome oxidase with Na+K+ATPase, NADPH-diaphorase, nitric oxide synthase, and N-methyl-D-aspartate receptor subunit 1. 950 44

A rapid method (about 1.5 h) for the isolation of intact functional mitochondria from neurons and astrocytes in primary culture is described. Mitochondria isolated by this method are metabolically active and tightly coupled as shown by respiratory control ratio values, which were about 4 with glutamate-malate as substrate. The activities of marker enzymes revealed the occurrence of a low degree of cytosolic (5%) or synaptosomal (5.5%) contamination in the mitochondrial fractions. In addition, the activity of citrate synthase was increased by 4 fold in both neuronal and astrocytic mitochondria with respect to values found in cell homogenates. These results confirm that the method affords mitochondrial preparations from cultured brain cells at suitable levels of purity and enrichment for the study of their mitochondrial function. Since mitochondrial damage has been associated with the pathogenesis of certain neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases (P. Chagnon, C. Betard, Y. Robitaille, A. Cholette, D. Gauvreau, Distribution of brain cytochrome oxidase activity in various neurodegenerative disease, Neuroreport 6 (1995) 711-715 [6]; S.J. Kish, C. Bergeron, A. Rajput, S. Dozic, F. Mastrogiacomo, L. Chang, J.M. Wilson, L.M. DiStefano, J.N. Nobrega, Brain cytochrome oxidase in Alzheimer's disease, J. Neurochem. 59 (1992) 776-779 [10]; A.H.V. Schapira, J.M. Cooper, D. Dexter, J.B. Clark, P. Jenner, C.D. Marsden, Mitochondrial complex I deficiency in Parkinson's disease, J. Neurochem. 54 (1990) 823-827 [15]), the method described here shed light on the possible susceptibility of neuronal or astrocytic mitochondria to deleterious effects of these diseases.
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PMID:A rapid method for the isolation of metabolically active mitochondria from rat neurons and astrocytes in primary culture. 950 34

We determined the ability of pathological levels of nitric oxide (NO) to cause glutamate release from isolated rat brain nerve terminals using a fluorometric assay. It was found that NO (0.7 and 2 microM) produced (4 and 10 nmol/mg of synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after 1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+-independent glutamate release. Preincubation of synaptosomes with 5 microM 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+-independent glutamate release produced by NO was greater in a low-oxygen medium. NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration with a similar order of potency with respect to their ability to cause glutamate release. Because NO has been shown previously to inhibit reversibly cytochrome oxidase in competition with oxygen, our findings in this study suggest that NO (and cyanide) causes glutamate release following inhibition of mitochondrial respiration at the level of cytochrome oxidase. Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicty may contribute to neuronal death in neurological diseases.
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PMID:Nitric oxide causes glutamate release from brain synaptosomes. 952 71


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