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)

We have investigated the mechanism of mitochondrial-nuclear crosstalk during cellular stress in mouse C2C12 myocytes. For this purpose, we used cells with reduced mitochondrial DNA (mtDNA) contents by ethidium bromide treatment or myocytes treated with known mitochondrial metabolic inhibitors, including carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimycin, valinomycin and azide. Both genetic and metabolic stresses similarly affected mitochondrial membrane potential (Deltapsim) and electron transport-coupled ATP synthesis, which was also accompanied by an elevated steady-state cytosolic Ca2+ level ([Ca2+]i). The mitochondrial stress resulted in: (i) an enhanced expression of the sarcoplasmic reticular ryanodine receptor-1 (RyR-1), hence potentiating the Ca2+ release in response to its modulator, caffeine; (ii) enhanced levels of Ca2+-responsive factors calineurin, calcineurin-dependent NFATc (cytosolic counterpart of activated T-cell-specific nuclear factor) and c-Jun N-terminal kinase (JNK)-dependent ATF2 (activated transcription factor 2); (iii) reduced levels of transcription factor, NF-kappaB; and (iv) enhanced transcription of cytochrome oxidase Vb (COX Vb) subunit gene. These cellular changes, including the steady-state [Ca2+]i were normalized in genetically reverted cells which contain near-normal mtDNA levels. We propose that the mitochondria-to-nucleus stress signaling occurs through cytosolic [Ca2+]i changes, which are likely to be due to reduced ATP and Ca2+ efflux. Our results indicate that the mitochondrial stress signal affects a variety of cellular processes, in addition to mitochondrial membrane biogenesis.
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PMID:Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. 992 12

The effect of caloric restriction (CR) initiated in adult rats (17 months of age) on the abundance of deleted mitochondrial genomes, mitochondrial enzymatic abnormalities, and fiber number was examined in rat skeletal muscle. Vastus lateralis muscle from young (3-4 months) ad libitum-fed, old (30-32 months) restricted (35% and 50% CR, designated CR35 and CR50, respectively), and old ad libitum-fed rats (29 months) was studied. CR preserved fiber number and fiber-type composition in the CR50 rats. In the old rats from all groups, individual fibers were found with either no detectable cytochrome-c oxidase activity (COX-), hyperactive for succinate dehydrogenase activity (SDH++), or both COX- and SDH++. Muscle from the CR50 rats contained significantly fewer COX- and SDH++ fibers than did the muscle from the CR35 rats. CR50 rats also had significantly lower numbers of mtDNA deletion products in two (adductor longus and soleus) of the four muscles examined compared to CR35 rats. These data indicate that CR begun in late middle age can retard age-associated fiber loss and fiber-type changes as well as lower the number of skeletal muscle fibers exhibiting mitochondrial enzyme abnormalities. CR can also decrease the accumulation of deleted mitochondrial genomes.
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PMID:Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice. 992 29

Controversy exists as to the clinical importance, cause, and disease specificity of the cytochrome oxidase (CO) activity reduction observed in some patients with Alzheimer's disease (AD). Although it is assumed that the enzyme is present in normal amount in AD, no direct measurements of specific CO protein subunits have been conducted. We measured protein levels of CO subunits encoded by mitochondrial (COX I, COX II) and nuclear (COX IV, COX VIc) DNA in autopsied brain of patients with AD whom we previously reported had decreased cerebral cortical CO activity. To assess disease specificity, groups of patients with spinocerebellar ataxia type I and Friedreich's ataxia were also included. As compared with the controls, mean protein concentrations of all four CO subunits were significantly decreased (-19 to -47%) in temporal and parietal cortices in the AD group but were not significantly reduced (-12 to -17%) in occipital cortex. The magnitude of the reduction in protein levels of the CO subunits encoded by mitochondrial DNA (-42 to -47%) generally exceeded that encoded by nuclear DNA (-19 to -43%). In the spinocerebellar ataxia disorders, COX I and COX II levels were significantly decreased in cerebellar cortex (-22 to -32%) but were normal or close to normal in cerebral cortex, an area relatively unaffected by neurodegeneration. We conclude that protein levels of mitochondrial- and nuclear-encoded CO subunits are moderately reduced in degenerating but not in relatively spared brain areas in AD and that the decrease is not specific to this disorder. The simplest explanation for our findings is that CO is decreased in human brain disorders as a secondary event in brain areas having reduced neuronal activity or neuronal/synaptic elements consequent to the primary neurodegenerative process.
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PMID:Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change? 993 Jul 43

Recent reports have suggested that mitochondrial dysfunction may contribute to the progression of the pathology of Alzheimer's disease (AD). However, both increases and decreases in the activity of cytochrome oxidase have been described in the hippocampi of AD patients. In this study we used immunohistochemistry and quantitative autoradiographic methods to study the expression pattern of two cytochrome oxidase subunit proteins (nuclear-encoded COX IV and mitochondrial-encoded COX I) in the hippocampus in relation to the development of AD-type pathology. We found heterogeneous expression of both COX subunits in AD with an increased expression of both subunit proteins in healthy, non-tangle-bearing, neurones but absence of both subunit proteins in tangle-bearing neurones. Levels of COX IV but not of COX I were related to the amount of hyperphosphorylated tau accumulated in the same hippocampal region but not to the amount of amyloid deposited in sporadic AD. In Down's syndrome COX I and COX IV were similarly increased in the presence of AD pathology in non-tangle-bearing neurones. However, in these cases levels of enzyme expression were correlated to the amount of amyloid accumulation but not the amount of hyperphosphorylated tau in the hippocampus. We believe that heterogeneity of expression of mitochondrial enzyme proteins between neurones may contribute to the conflicting conclusions in previous reports regarding relative levels of cytochrome oxidase activity in the hippocampus in AD. We hypothesise that the increased mitochondrial enzyme expression in healthy-appearing neurones of AD brains may represent a physiological response to increased functional demand on surviving neurones as a consequence of AD-related neuronal pathology.
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PMID:Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology. 1020 73

In the present study, we have applied a novel strategy involving the postmortem measurement of the mitochondrial respiratory chain enzyme cytochrome-c oxidase (COX; complex IV) to identify regional changes in energy metabolism in the basal ganglia of chronic, medicated schizophrenics. COX activity was decreased in the caudate nucleus but increased in the putamen and nucleus accumbens. An increase in succinate dehydrogenase (complex II) was evident in the putamen and nucleus accumbens, but changes were not seen with NADH dehydrogenase (complex I). An analysis of interregional correlations in energy metabolism revealed several anomalies in the connections between the caudate and putamen and the globus pallidus in schizophrenics. Results provide strong evidence that changes in baseline energy metabolism in specific regions of the basal ganglia may exist in the disease. Based upon the high degree of input it receives from associative cortical areas, results suggest that a defect in the caudate may underlie certain aspects of cognitive decline in schizophrenics. In contrast, an increase in COX in the putamen, which receives extensive projections from the sensorimotor cortex, may reflect an effect of chronic neuroleptic treatment on motor function.
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PMID:Mitochondrial function is differentially altered in the basal ganglia of chronic schizophrenics. 1045 34

The oxidative capacity of the liver, the heart and skeletal muscles for fatty acids were investigated in preruminant calves fed for 19 d on a milk-replacer containing either coconut oil (CO, rich in 12:0) or tallow (rich in 16:0 and 18:1). Weights of the total body and tissues did not differ significantly between the two groups of animals but plasma glucose and insulin concentrations were lower in the CO group. Feeding on the CO diet induced an 18-fold increase in the hepatic concentration of triacylglycerols. Rates of total and peroxisomal oxidation of [1-14C]laurate, [1-14C]palmitate and [1-14C]oleate were measured in fresh tissue homogenates. Higher rates of total oxidation in liver homogenate and of peroxisomal oxidation in liver, heart and rectus abdominis muscle homogenates were observed with laurate used as substrate. Furthermore, the relative contribution of peroxisomes to total oxidation was 1.9-fold higher in the liver and in the heart with laurate than with oleate or palmitate. Finally, the peroxisomal oxidation rate of oleate was 1.5-fold higher in the hearts of calves fed on the CO diet. Whatever the tissue, citrate synthase (CS, EC 4.1.3.7) and cytochrome c oxidase (COX, EC 1.9.3.1) activities were similar between the two groups of calves but the COX: CS activity ratio was lower in the liver of the CO group. In conclusion, laurate is better catabolized by peroxisomes than long-chain fatty acids, especially in the liver. Elongation of lauric acid after partial oxidation might explain the hepatic triacylglycerol accumulation in calves fed on the CO diet.
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PMID:Effects of dietary coconut oil on fatty acid oxidation capacity of the liver, the heart and skeletal muscles in the preruminant calf. 1065 79

To assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, complexes II+III, complex IV (cytochrome c oxidase, COX), succinate dehydrogenase, and citrate synthase in the frontal cortex, temporal cortex, hippocampus, and cerebellum of 23 AD patients and 13 normal human brains. The major finding was a significant decrease in COX activity in AD temporal cortex and hippocampus, both whether activities were expressed per noncollagen protein content (49 +/-4.6 versus 78+/-10.8 nmol/min/mg NCP, P = 0.006; 23+/-1.9 versus 48.6+/-8.1 nmol/min/mg NCP, p = 0.003) or corrected for citrate synthase activity (1.6+/-0.2 versus 3+/-0.4, P = 0.001; 0.76+/-0.1 versus 1.76+/-0.26, P = 0.0009). There were no significant differences in the activities of complexes I+III, II+III, and of succinate dehydrogenase in any of the brain regions examined. Our results suggest a specific defect of COX in the AD brain versus the normal human brain, which may contribute to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity.
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PMID:A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. 1085 95

A fluorogenic (TaqMan) PCR assay was developed to detect Ralstonia solanacearum strains. Two fluorogenic probes were utilized in a multiplex reaction; one broad-range probe (RS) detected all biovars of R. solanacearum, and a second more specific probe (B2) detected only biovar 2A. Amplification of the target was measured by the 5' nuclease activity of Taq DNA polymerase on each probe, resulting in emission of fluorescence. TaqMan PCR was performed with DNA extracted from 42 R. solanacearum and genetically or serologically related strains to demonstrate the specificity of the assay. In pure cultures, detection of R. solanacearum to >/=10(2) cells ml(-1) was achieved. Sensitivity decreased when TaqMan PCR was performed with inoculated potato tissue extracts, prepared by currently recommended extraction procedures. A third fluorogenic probe (COX), designed with the potato cytochrome oxidase gene sequence, was also developed for use as an internal PCR control and was shown to detect potato DNA in an RS-COX multiplex TaqMan PCR with infected potato tissue. The specificity and sensitivity of the assay, combined with high speed, robustness, reliability, and the possibility of automating the technique, offer potential advantages in routine indexing of potato tubers and other plant material for the presence of R. solanacearum.
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PMID:Detection of Ralstonia solanacearum strains with a quantitative, multiplex, real-time, fluorogenic PCR (TaqMan) assay. 1087 78

Previous studies in our laboratory demonstrated significant changes in bovine heart mitochondrial bioenergetics during fetal growth and development. To further understand mitochondrial biogenesis in early human development, the activity and subunit content levels of specific mitochondrial enzymes in fetal and neonatal heart were determined. Comparing early gestation (EG, 45-65 day) later gestation (LG, 85-110 day) and neonate (birth-1 month), specific activity of citrate synthase (CS), a Krebs cycle enzyme showed a 2 fold increase from EG to LG and a 2 fold increase from LG to neonate. Specific activities of complex IV and complex V increased similarly 1.8-2 fold from EG to LG. However during the later fetal period from LG to neonate, complex IV activity increased only 1.3 fold and complex V showed no significant increase. Peptide content of COX-II subunit increased 2 fold from EG to LG and by 3.5 fold from LG to neonate. Levels of COX-IV and ATP synthase alpha subunits were undetectable in EG hearts, clearly detectable in LG heart and 3 fold increased from LG to neonate. Unexpectedly, mitochondrial transcription factor A (mt-TFA) levels were not significantly different during these developmental stages. Mitochondrial DNA (mtDNA) levels increased 1.8 fold from EG to LG, and 3.8 fold increase from EG to neonate and correlated with CS activity levels. In conclusion, these data indicate coordinated regulation of some nuclear-encoded (COX-IV and CS activity) and mitochondrial components (COX-II and mtDNA), and strongly suggest that mitochondrial content increases particularly during the early fetal cardiac development and reveal a distinct pattern of regulation for mt-TFA.
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PMID:Heart mitochondrial DNA and enzyme changes during early human development. 1097 57

Eucaryotic cells contain at least two general classes of oxygen-regulated nuclear genes: aerobic genes and hypoxic genes. Hypoxic genes are induced upon exposure to anoxia while aerobic genes are down-regulated. Recently, it has been reported that induction of some hypoxic nuclear genes in mammals and yeast requires mitochondrial respiration and that cytochrome-c oxidase functions as an oxygen sensor during this process. In this study, we have examined the role of the mitochondrion and cytochrome-c oxidase in the expression of yeast aerobic nuclear COX genes. We have found that the down-regulation of these genes in anoxic cells is reflected in reduced levels of their subunit polypeptides and that cytochrome-c oxidase subunits I, II, III, Vb, VI, VII, and VIIa are present in promitochondria from anoxic cells. By using nuclear cox mutants and mitochondrial rho(0) and mit(-) mutants, we have found that neither respiration nor cytochrome-c oxidase is required for the down-regulation of these genes in cells exposed to anoxia but that a mitochondrial genome is required for their full expression under both normoxic and anoxic conditions. This requirement for a mitochondrial genome is unrelated to the presence or absence of a functional holocytochrome-c oxidase. We have also found that the down-regulation of these genes in cells exposed to anoxia and the down-regulation that results from the absence of a mitochondrial genome are independent of one another. These findings indicate that the mitochondrial genome, acting independently of respiration and oxidative phosphorylation, affects the expression of the aerobic nuclear COX genes and suggest the existence of a signaling pathway from the mitochondrial genome to the nucleus.
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PMID:Effects of anoxia and the mitochondrion on expression of aerobic nuclear COX genes in yeast: evidence for a signaling pathway from the mitochondrial genome to the nucleus. 1109 3


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