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)

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

To gain a better understanding of the potential role of altered gene expression in the diminished muscle function in old age, we performed a broad search for transcripts expressed at quantitatively different levels in younger (21-24 yr) and older (66-77 yr) human vastus lateralis muscle by serial analysis of gene expression (SAGE). Because SAGE was based on RNA pooled from muscle of several different subjects, relative concentrations of selected mRNAs also were determined in individual muscle samples by quantitative RT-PCR. There were 702 SAGE tags detected at least 10 times in one or both mRNA pools, and the detection frequency was different (at P < 0.01) between young and older muscle for 89 of these. The ratio of myosin heavy chain 2a mRNA to myosin heavy chain 1 mRNA was reduced in older muscle. The mRNAs encoding several mitochondrial proteins involved in electron transport (including several subunits of cytochrome-c oxidase and NADH dehydrogenase) and subunits of ATP synthase were approximately 30% less abundant in older muscle. Several mRNAs encoding enzymes involved in glucose metabolism also were less abundant in older muscle. Analysis of individual samples revealed that the differences suggested by SAGE were not artifacts of atypical gene expression in one or a few individuals. These data suggest that some of the phenotypic changes in senescent muscle may be related to altered gene transcription.
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PMID:High-abundance mRNAs in human muscle: comparison between young and old. 1090 65

Nitric oxide synthase-1 (NOS-1) is found in high concentrations in skeletal muscles, where its synthesis product nitric oxide (NO) is reported to be involved in a number of processes, including the modulation of the oxidative metabolism of myofibers. Performing immunoblot analysis and quantification of formazan produced by its specific NADPH diaphorase activity, we found NOS-1 to be enriched in rat skeletal muscles with a high proportion of fast-twitch myofibers. Since these myofibers represent a metabolically heterogeneous subpopulation, we extended our investigation to the level of individual myofibers. Using serial sections we combined myosin heavy chain-based fiber-typing with quantitative succinate dehydrogenase histochemistry to determine three groups of fiber-types, comprising fast-oxidative, fast-glycolytic and slow-oxidative myofibers. Image analysis showed that NOS-1 diaphorase activity is significantly enriched in fast-oxidative myofibers compared with fast-glycolytic and slow-oxidative ones. In order to characterize potential biological effects of the fiber-type-specific enrichment of NOS-1, we performed cytochrome oxidase histochemistry in the presence of the NO donors NOC-9 and SNAP. Both NO donors reduced cytochrome oxidase activity in all myofibers investigated with almost identical semi-maximal inhibition rates, although fast-oxidative and slow-oxidative myofibers contained twice as much basal catalytic activity than fast-glycolytic ones. In summary, we suggest that the NOS-1/NO system of skeletal muscles exerts its biological role especially in fast-oxidative myofibers, since these myofibers express more NOS-1 than fast-glycolytic or slow-oxidative ones and also contain the highest concentrations of cytochrome oxidases as potential target molecules of NO.
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PMID:Nitric oxide synthase-1 is enriched in fast-twitch oxidative myofibers. 1170 44

We evaluated the effects of testosterone overload on mitochondrial superoxide dismutase (MnSOD), cytochrome oxidase (COX) and citrate synthase (CS) activities of the rat superficial gastrocnemius both in non-exercised muscle and following moderate endurance training. Basal (bLPO) and stimulated (sLPO) lipid peroxidation was measured as an index of oxidative tissue damage. Furthermore, to assess the relationship between exercise and testosterone-induced metabolic adaptations and contractile protein expression, the distribution of myosin heavy chain (MHC) isoforms was analysed by SDS-PAGE. Samples were obtained from: controls (C), rats treated with testosterone propionate (Tp) (TP, 5 mg kg(-1) i.m. 6 days/week), trained rats (E, 5 days/week) and rats trained and treated with Tp (ETP). MnSOD significantly increased in E and TP in comparison with C and ETP. Training induced a significant increase in COX activity both in E and ETP whereas a statistical reduction was observed in TP in comparison with the other groups. Moreover, testosterone administration was associated with a significant reduction in CS activity which significantly increased in ETP. A reduction in lipid peroxidation was observed in E and ETP in comparison with controls both in basal and stimulated conditions, whereas TP showed a significant increase of bLPO. In trained rats enzymatic changes were correlated with an increase in the proportion of fast oxidative MHC-2A and MHC-2X with decrease of the proportion of fast MHC-2B. In contrast, Tp treatment induced an increase in the proportion of MHC-2B whereas MHC-2A and MHC-2X disappeared. Finally, ETP showed a reduction in MHC-2B and an increase in MHC-1 and MHC-2X. These data suggest that testosterone supplementation seems not to significantly modify the metabolic adaptation induced by exercise in gastrocnemius muscle. Furthermore, testosterone overload to non-exercised rats seems to reduce the mitochondrial function and increase the lipid peroxidation of the muscle.
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PMID:"Oxidative stress": effects of mild endurance training and testosterone treatment on rat gastrocnemius muscle. 1235 95

Gene expression changes in the corpus cavernosum of hypercholesterolemic rats were not fully assessed, which were not previously known to be associated with hypercholesterolemia-related erectile dysfunction (ED). To provide molecular insight into pathophysiology of hypercholesterolemia-related ED and to investigate the effects of Udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using GenoCheck platinum cDNA chip (Ansan, S. Korea). Sixteen male Sprague-Dawley rats were fed 2% cholesterol diet for 5 months. Half of them were orally treated with Udenafil (20 mg/kg/day) simultaneously. Eight age-matched rats fed normal diet were served as normal control. RNA was extracted from corpus cavernosum and microarray analysis was performed. Decreased erectile responses and hypercholesterolemia were observed in hypercholesterolemic control group. In microarray analysis, 122 candidate genes were noted to be altered based on the magnitude of expression changes, which includes 44 down-regulated and 78 up-regulated genes compared with the age-matched normal controls. These changes were, however, significantly attenuated by treatment with Udenafil. Out of the 78 up-regulated genes, 8 genes were significantly decreased by the chronic treatment with Udenafil. The altered genes were cytochrome oxidase biogenesis protein OXA1, skeletal muscle myosin heavy chain, lipophilin, fast skeletal muscle isoforms beta/alpha, myosin light chain 3, cytochrome c oxidase, adipocyte fatty acid binding protein and one EST gene. In contrast, among the 44 down-regulated genes, Kruppel-like factor 5 and cyclin D1 genes were increased after the Udenafil treatment. These results provide the molecular basis for understanding the pathogenesis of hypercholesterolemia-related ED and offer clues on determining the underlying action mechanism of a PDE5 inhibitor.
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PMID:Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor. 1713 5

Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats. Animals with severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal heart failure or were euthanized because of age-related complications. Exercise delayed mortality resulting from heart failure (P<0.001) and all causes (P<0.05) and transiently attenuated the systolic hypertension and contractile dysfunction observed in the sedentary animals but had no effect on cardiac morphology or contractile function in end-stage heart failure. Training had no effect on terminal myocardial protein expression of antioxidant enzymes, calcium handling proteins, or myosin heavy chain isoforms but was associated with higher cytochrome oxidase activity in cardiac mitochondria (P<0.05) and a greater mitochondrial content of cardiolipin, a phospholipid that is essential for optimal mitochondrial energy metabolism. In conclusion, low-intensity exercise training significantly delays the onset of heart failure and improves survival in female hypertensive heart failure rats without eliciting sustained improvements in blood pressure, cardiac function, or expression of several myocardial proteins associated with the cardiovascular benefits of exercise. The effects of exercise on cytochrome oxidase and cardiolipin provide novel evidence that training may improve prognosis in hypertensive heart disease by preserving mitochondrial energy metabolism.
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PMID:Low-intensity exercise training delays heart failure and improves survival in female hypertensive heart failure rats. 1825 16

Tropical marine habitats often harbor high biodiversity, including many cryptic taxa. Though the prevalence of cryptic marine taxa is well known, the evolutionary histories of these groups remain poorly understood. The snapping shrimp genus Alpheus is a good model for such investigations, as cryptic species complexes are very common, indicating widespread genetic diversification with little or no morphological change. Here, we present an extensive phylogeographic investigation of the diversified amphi-American Alpheus armillatus species complex, with geographic sampling in the Caribbean Sea, Gulf of Mexico, Florida, Brazil, and the tropical Eastern Pacific. Sequence data from two mitochondrial genes (16SrRNA and cytochrome oxidase I) and one nuclear gene (myosin heavy chain) provide strong evidence for division of the species complex into six major clades, with extensive substructure within each clade. Our total data set suggests that the A. armillatus complex includes no less than 19 putative divergent lineages, 11 in the Western Atlantic and 8 in the Eastern Pacific. Estimates of divergence times from Bayesian analyses indicate that the radiation of the species complex began approximately 10 MYA with the most recent divergences among subclades dating to within the last 3 MY. Furthermore, individuals from the six major clades had broadly overlapping geographic distributions, which may reflect secondary contact among previously isolated lineages, and have apparently undergone several changes in superficial coloration, which is typically the most pronounced phenotypic character distinguishing lineages. In addition, the extensive substructure within clades indicates a great deal of molecular diversification following the rise of the Isthmus of Panama. In summary, this investigation reflects substantial biodiversity concealed by morphological similarity, and suggests that both ancient and ongoing divergences have contributed to the generation of this biodiversity. It also underlines the necessity to work with the most complete data set possible, which includes comprehensive and wide-ranging sampling of taxa.
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PMID:Molecular phylogeny reveals extensive ancient and ongoing radiations in a snapping shrimp species complex (Crustacea, Alpheidae, Alpheus armillatus). 1904 48

To investigate the molecular basis of temperature adaptation in natural populations we used the candidate gene approach, targeting the myosin heavy chain (MyHC) gene. The functional effects of genetic variation in MyHC have been well characterised, and changes in the flexibility of the surface loops 1 and 2, caused by modulations in length, amino acid composition and charge can play an important role in thermal acclimation in fish. However, the extent that MyHC diversity is influenced by natural thermal gradients is largely unknown. Sequence variation in MyHC cDNA was examined in 7 species of gammarid amphipod with broad latitudinal distributions and differing intertidal thermal habitats in the NE Atlantic and Arctic Oceans. A high degree of diversity was detected in the loop 1 nucleotide sequences, although not all are likely to be functional transcripts, and their deduced amino acid sequences indicated no differences in the length and charge of loop 1 and associated binding kinetics. Four isoforms for loop 2 were detected which differed in sequence length and charge distribution, suggesting functional differences in sliding velocities and ATPase activities. While all species, and indeed most individuals, expressed multiple loop 2 isoforms, analysis of the two species with the greatest number of sequenced clones revealed that G. duebeni, a high-shore species with the highest thermal tolerance, expressed a greater diversity of forms than G. oceanicus, a low intertidal species more sensitive to temperature change. Latitude further influenced MyHC loop 2 diversity in G. duebeni, as the number of isoforms increased in the northern populations. Species-specific variations in MyHC diversity were observed, irrespective of phylogenetic associations revealed by analysis of the mitochondrial cytochrome oxidase 1 (CO1) gene. Overall, it appears that the temporal temperature variations associated with higher intertidal habitat may be a greater selective agent for MyHC isoform diversity in gammarid muscles than broad spatial changes with latitude.
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PMID:Linking functional molecular variation with environmental gradients: myosin gene diversity in a crustacean broadly distributed across variable thermal environments. 1923 10

Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (Vo(2max)) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed Vo(2max) tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, and repeat Vo(2max) testing on day 8. Six independent subjects underwent CO breathing and two muscle biopsies without exercise testing. Molecular studies were performed by real-time RT-PCR, Western blot analysis, and immunochemistry. After Vo(2max) testing plus CO breathing, significant increases were found in mRNA levels for nuclear respiratory factor-1, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, mitochondrial transcription factor-A (Tfam), and DNA polymerase gamma (Polgamma) with no change in mitochondrial DNA (mtDNA) copy number or Vo(2max). Levels of myosin heavy chain I and nuclear-encoded HO-1, superoxide dismutase-2, citrate synthase, mitofusin-1 and -2, and mitochondrial-encoded cytochrome oxidase subunit-I (COX-I) and ATPase-6 proteins increased significantly. None of these responses were reproduced by Vo(2max) testing alone, whereas CO alone increased Tfam and Polgamma mRNA, and COX-I, ATPase-6, mitofusin-2, HO-1, and superoxide dismutase protein. These findings provide evidence linking the HO/CO response involved in mitochondrial biogenesis in rodents to skeletal muscle in humans through a set of responses involving regulation of the mtDNA transcriptosome and mitochondrial fusion proteins autonomously of changes in exercise capacity.
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PMID:Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans. 1946 54

Although most literature suggests a relative protection of slow twitch muscle with aging, there is limited data in senescence when muscle atrophy and functional decline markedly accelerate. To address this issue we examined age-related changes in muscle mass, contractile function, mitochondrial enzyme activities, and myosin heavy chain (MHC) expression in the slow twitch soleus (Sol) and fast twitch gastrocnemius (Gas) muscle of young adult (YA) and senescent (SEN) rats. Muscle mass declined between YA and SEN in the Sol by 35% compared to 55% in the Gas muscle. After normalizing for muscle mass, tetanic force per g of muscle declined by 58% in Sol and by 36% in Gas muscle. Time-to-peak tension was increased only in the Gas (30%), whereas time-to-half relaxation was increased by 70% in Sol and 51% in Gas. Citrate synthase and complex IV activity declined in homogenates of Sol (30-36%) and red oxidative region of Gas (46-51%), but not white glycolytic region of Gas. Strikingly, the shift away from the dominant adult MHC isoform with aging was much greater in Sol (fibers positive for MHC fast: 11+/-2% in YA versus 36+/-3% in SEN) than in Gas (fibers positive for MHC slow: 12+/-1% in YA versus 26+/-3% in SEN) muscle. Collectively, these results show that the slow twitch Sol muscle undergoes large phenotypic alterations in very old age and for several measures (tetanic tension per g, time-to-half relaxation and shift in adult MHC expression) that is of greater magnitude than fast twitch muscle, underscoring the importance of including age-related changes in slow twitch muscle in seeking potential treatments for sarcopenia.
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PMID:Slow twitch soleus muscle is not protected from sarcopenia in senescent rats. 2039 45


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