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)

The aim of this study was to evaluate the effect of lead and excess zinc on the adaptation of mitochondria from skeletal muscles to physical effort. Rats were intoxicated once a week for 12 weeks by subcutaneous injection of the solution containing 2 mg Zn+2 and/or 3 mg Pb2+ per kg of body weight. During the last 6 weeks, 6 times weekly, rats performed endurance training which involved swimming 15 minutes daily with additional load of 5% of the body weight. The activities of isocitrate (ICD), malate (SDH), succinate (MDH) dehydrogenases, cytochrome oxidase (COX) and protein content (PM) were determined in the mitochondrial fractions obtained from the soleus muscle (ST fibres), and from the superficial (FTb fibres) and deep (FTa fibres) parts of the gastrocnemius muscle. In the control group (C), which was injected with saline, higher activities of ICD and MDH were obtained in FTa and FTb fibres than in the ST fibres. SDH and COX had higher activities in FTa and ST compared to FTb fibres. Zinc treatment (Zn) caused diminution of ICD, SDH and COX activities in ST fibres. Lead intoxication (Pb) resulted in a decrease of MDH activity in all fibre types, and in a decrease of SDH activity in ST fibres. Simultaneous action of zinc and lead produced an increase in ICD activity and diminution of COX activity in FTb fibres. It also resulted in an increase of SDH and decrease of COX activity in ST fibres. These results suggest that the ST fibres are more susceptible to disturbances of adaptation to physical exercise caused by zinc and lead. There are no signs of uniform antagonism between zinc and lead action in the processes under investigation.
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PMID:The activity of mitochondrial enzymes in the muscles of rats subjected to physical training and subchronical intoxication with lead and zinc. 248 52

The gastric mucosa of marmosets is devoid of UDPG-GT; phosphorylases; G-6-PA; F-1,6-PA; alanyl aminopeptidase and leucine aminopeptidase. Only the acid phosphatase was seen with a stronger reactivity in the chief cells. The other enzymes (LDH; G-6-PDH; 6-PGDH; NADPH2-TR; cis-aconitase; ICDH; SDH; MDH; cytochrome oxidase; NADH2-TR; a-GPDH; b-OHBDH and nonspecific esterase) showed a stronger reactivity in the parietal cells.
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PMID:[Histoenzymologic data on the epithelial cells of the gastric mucosa of marmosets (Callithrix jacchus & Callithrix penicillata)]. 677 86

This article reports a new MERRF family. The mother, regarded as suffering from Ramsay-Hunt Syndrome, and her three daughters, had the same clinical pattern: myoclonic epilepsy and ataxia. Two daughters were studied on morphological, biochemical and molecular genetic levels. Muscle biopsies showed ragged-red fibres and mitochondrial vasculopathy. Arterioles were strongly SDH-reactive and COX-negative. By electron microscopy, abnormal mitochondria were observed in skeletal muscle fibres, in smooth muscle fibres of intramuscular vessels and in sweat gland epithelium. The study of the respiratory chain showed complex IV and I + IV deficiency, respectively. Mitochondrial tRNA (lys) mutation at position 8344 was pointed out as previously reported in the MERRF syndrome.
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PMID:Merrf family with 8344 mutation in tRNA (lys). Evidence of a mitochondrial vasculopathy in muscle biopsies. 818 18

The authors report the case of a female patient, 18 years of age, with slowly progressing weakness in upper and lower limbs since childhood. There were no significant antecedents. The neurologic examination showed mild proximal and distal motor deficit with a slight muscular retraction at the level of shoulders, elbows, coxofemural joints, knees and ankles; muscular hypotrophy in the legs and feet; reflexes were present and sensitivity was normal. Creatinephosphokinase showed an increase of one and a half times the normal value. Electroneuromyography: decrease in the amplitude and duration of action potentials and excessive recruitment of motor units, compatible with a primary muscular disease. A muscle biopsy with frozen sections (HE, Gomori, PAS, ATPases, NADH, SDH, acid and alcaline phosphatases, cytochrome oxidase and Oil-red-o) revealed a primary muscular disease characterized by the presence of nemalinic and intracytoplasmic spheroid bodies. Nemalinic bodies have been described with different structural abnormalities of muscle fibers; however, such association is rare. This is the second case report of concomitant occurrence of nemalinic and spheroid bodies.
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PMID:[Nemalinic myopathy with intracytoplasmic spheroid bodies: report of a case]. 873 55

Zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) are the reference antiretroviral therapy in patients with AIDS. A toxic mitochondrial myopathy can be observed in patients treated with AZT, but not with ddI and ddC. All 3 compounds can inhibit mitochondrial (mt)DNA polymerase and cause termination of synthesis of growing mtDNA strands and mtDNA depletion. The propensity to injure particular target tissues is unexplained. In our work, cultured muscle cells prepared from human muscle biopsies, were exposed to various concentrations of AZT (4-5000 micromol/l), ddI (5-1000 micromol/l) and ddC (1-1000 micromol/l) for 10 days. We evaluated cell proliferation and differentiation and measured lipid droplet accumulation, lactate production and respiratory chain enzyme activities. All 3 compounds induced a dose-related decrease of cell proliferation and differentiation. AZT seemed to be the most potent inhibitor of cell proliferation. AZT, ddI and ddC induced cytoplasmic lipid droplet accumulations, increased lactate production and decreased activities of COX (complex IV) and SDH (part of complex II). NADHR (complex I) and citrate sinthase activities were unchanged. Zalcitabine (ddC) and, to a lesser extent, ddI, were the most potent inhibitors of mitochondrial function. In conclusion, AZT, ddI and ddC all exert cytotoxic effects on human muscle cells and induce functional alterations of mitochondria possibly due to mechanisms other than the sole mtDNA depletion. Our results provide only a partial explanation of the fact that AZT, but not ddI and ddC, can induce a myopathy in HIV-infected patients. AZT myopathy might not simply result from a direct mitochondrial toxic effect of crude AZT.
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PMID:Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells. 916 61

Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.
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PMID:[MNGIE syndrome in 2 siblings]. 968 18

The hypothesis that mitochondrial dysfunction contributes to the senescent loss of skeletal muscle was investigated in quadriceps from 2- to 39-year old rhesus monkeys. Histological approaches, both cross-sectional (a single cross-section of the muscle) and longitudinal (multiple cross-sections of individual fibers spanning a 350-1600 microm region), were used to identify muscle fibers with abnormal mitochondrial electron transport system (ETS) enzyme activities and mitochondrial DNA deletions. Fibers were examined for two ETS activities, succinate dehydrogenase (SDH, ETS complex II) and cytochrome c oxidase (COX, ETS complex IV). The number of individual fibers containing ETS abnormalities (predominately negative for cytochrome c oxidase activity and/or hyperreactive for succinate dehydrogenase) increased with age. Deletions of the mitochondrial genome were observed in 89% of these ETS abnormal fibers. Longitudinal analysis allowed characterization of the ETS abnormal phenotype along their length. A decrease in cross-sectional area in 14% of the ETS abnormal fibers supports the hypothesis that deleted mitochondrial genomes may contribute to age-related fiber atrophy.
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PMID:Association of age-related mitochondrial abnormalities with skeletal muscle fiber atrophy. 984 Jul 42

Respiratory oxidative phosphorylation represents a central functionality in plant metabolism, but the subunit composition of the respiratory complexes in plants is still being defined. Most notably, complex II (succinate dehydrogenase) and complex IV (cytochrome c oxidase) are the least defined in plant mitochondria. Using Arabidopsis mitochondrial samples and 2D Blue-native/SDS-PAGE, we have separated complex II and IV from each other and displayed their individual subunits for analysis by tandem mass spectrometry and Edman sequencing. Complex II can be discretely separated from other complexes on Blue-native gels and consists of eight protein bands. It contains the four classical SDH subunits as well as four subunits unknown in mitochondria from other eukaryotes. Five of these proteins have previously been identified, while three are newly identified in this study. Complex IV consists of 9-10 protein bands, however, it is more diffuse in Blue-native gels and co-migrates in part with the translocase of the outer membrane (TOM) complex. Differential analysis of TOM and complex IV reveals that complex IV probably contains eight subunits with similarity to known complex IV subunits from other eukaryotes and a further six putative subunits which all represent proteins of unknown function in Arabidopsis . Comparison of the Arabidopsis data with Blue-native/SDS-PAGE separation of potato and bean mitochondria confirmed the protein band complexity of these two respiratory complexes in plants. Two-dimensional Blue-native/Blue-native PAGE, using digitonin followed by dodecylmaltoside in successive dimensions, separated a diffusely staining complex containing both TOM and complex IV. This suggests that the very similar mass of these complexes will likely prevent high purity separations based on size. The documented roles of several of the putative complex IV subunits in hypoxia response and ozone stress, and similarity between new complex II subunits and recently identified plant specific subunits of complex I, suggest novel biological insights can be gained from respiratory complex composition analysis.
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PMID:Mitochondrial cytochrome c oxidase and succinate dehydrogenase complexes contain plant specific subunits. 1560 29

Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.
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PMID:Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine. 1633 77

Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F(1)beta subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F(1)beta differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.
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PMID:Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria. 1789 67


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