Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown the association of NOS I with the sarcolemma in mammalian striated muscle fibers, implicating the dystrophin complex (DC) as a major anchor for the enzyme. The potential role of the sarcoglycan subcomplex, especially of alpha-sarcoglycan (adhalin), as part of the DC in holding of NOS I in the sarcolemmal position was examined by carrying out a comparative study on the distribution of NOS I, dystrophin, dystrophin-associated glycoproteins (DAG) and alpha-sarcoglycan in various skeletal muscles of non-mammals. Rat muscles were included since they reflect the situation in mammals. Catalytic NOS-associated diaphorase (NOSaD) activity as well as NOS I and DAG immunoreactivities were positive in the saracolemma region of skeletal muscle fibers of rats, chicken, and turtles. Adhalin immunoreactivity was present in the rat but absent in the chicken and turtle muscle surface membrane. These data suggest that alpha-sarcoglycan and therefore the entire sarcoglycan subcomplex may not be needed for localizing NOS I to the sarcolemma in these non-mammalian species. This may hold for skeletal muscle fibers in general.
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PMID:Adhalin (alpha-sarcoglycan) is not required for anchoring of nitric oxide synthase I (NOS I) to the sarcolemma in non-mammalian skeletal (striated) muscle fibers. 886 63

Recently, it has been shown that in human striated muscle the signalling enzyme, brain-type nitric oxide synthase I (NOS I), is associated with the sarcolemma and complexes with dystrophin and/or members of the dystrophin complex. In order to find out whether there exists a regular association between NOS I and the complex, muscle biopsies from patients with various muscle disorders were analysed by enzyme histochemistry and immunohistochemistry. In patients suffering from Duchenne muscular dystrophy, and to a lesser extent in those with Becker-type dystrophy, NOS I and dystrophin complex components were absent or drastically reduced in the sarcolemma region. In other dystrophies, as well as in metabolic and inflammatory myopathies, NOS I and dystrophin complex constituents were expressed normally, while in the case of neurogenic diseases leading to denervation atrophy and especially congenital idiopathic clubfoot, the immunohistochemical patterns of the distribution of the dystrophin complex constituents were normal, but NOS I activity and protein were deficient or dramatically diminished. The results can be interpreted as indicating that, in general, NOS I targeting to the sarcolemma is dependent on particular members of the dystrophin complex, such as alpha-1 syntrophin, yet the expression and/or positioning of NOS I may be under the control of further factors, probably of neurogenic origin. NOS I-associated diaphorase may thus be a useful complementary tool in the diagnosis of muscle disorders.
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PMID:Absence of nitric oxide synthase I despite the presence of the dystrophin complex in human striated muscle. 914 66

As intrafusal nuclear bag and chain fibers of muscle spindles take part in both sensory and motor functions, these stretch receptors may represent a useful model to answer the question whether nitric oxide (NO) signalling is involved in sensory and motor functions or motor events only, as has already been shown for ordinary extrafusal fibers. To answer these questions, we have applied immunohistochemical and enzyme histochemical methods to serial transverse sections of the rat gastrosoleus muscle for determining the presence or absence of NOS I, NOS-associated diaphorase (NOSaD), AChE and proteins related to the dystrophin complex. NOS I, NOSaD, and AChE were practically absent from the equatorial (central) region of intrafusal fibers, i.e. the site of termination of the primary and secondary afferents. These regions showed weak staining for dystrophin, beta-dystroglycan as well as alpha- and gamma-sarcoglycan. By contrast, all of these molecules were found enriched in the polar (peripheral) regions of the intrafusal fiber sarcolemma. NOS I, NOSaD, dystrophin, beta-dystroglycan and the two sarcoglycans showed a general presence in the sarcolemma, whereas AChE was limited to the endplate region and other circumscribed areas. From these observations we would like to conclude that NO does not appear to be significantly or even not involved in signal transfer to the sensory nerve endings in the intrafusal fibers.
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PMID:NO is not substantially involved in afferent signalling in rat muscle spindles. 942 3

Recently, it has been shown for mouse skeletal muscle that caveolin-3 is localized in the sarcolemma and cofractionates with the original dystrophin complex (DC). In order to find out whether caveolin-3 is a further component of the recently established and enlarged nitric oxide synthase (NOS) I-DC and whether members of this complex interact with and are potentially regulated by caveolin-3, mammalian and non-mammalian healthy and diseased (dystrophic) skeletal muscles were investigated using caveolin-3, NOS I, DC components and myosin immunohistochemistry as well as NOS I-associated diaphorase histochemistry. In healthy mammalian skeletal muscle, caveolin-3 was colocalized with the DC components in all extra- and intrafusal fibers. By contrast, NOS I was absent in type I extrafusal fibers of certain species. In patients with Duchenne muscular dystrophy and mdx mice the components of the NOS I-DC were not detected in all extra- and intrafusal fiber types, while caveolin-3 was found unchanged. In healthy non-mammalian skeletal muscle, i.e. of birds, reptiles and fishes, caveolin-3 immunoreactivity was lacking in the sarcolemma as was alpha-sarcoglycan; the other NOS I-DC components were either present or absent. In conclusion, although caveolin-3 is localized in the sarcolemma of mammalian myofibers, there are differences in the microarchitecture of the components of the DC complex and of caveolin-3 which does not appear to be linked with the NOS I-DC. Potential regulatory interactions between caveolin-3 and NOS I may nevertheless exist in those fibers where both molecules are colocalized. The absence of caveolin-3 and alpha-sarcoglycan immunoreactivities in non-mammalian myofibers may suggest that the functions of these proteins are subserved by other components of NOS I-DC complex.
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PMID:Caveolin-3 and nitric oxide synthase I in healthy and diseased skeletal muscle. 954 84

The neuronal isoform of nitric oxide synthase (nNOS, termed also NOS-I) is expressed in normal adult skeletal muscle, suggesting important functions for NO in muscle biology. However, the expression and subcellular localization of NOS in muscle development and myoblast differentiation are largely unknown. In the present study, NOS was immunolocalized with isoform-specific antibodies in developing muscle and in differentiated myoblast cultures (mouse C2C12) together with histochemical NADPH-dependent diaphorase activity that is blocked by specific NOS inhibitors and therefore designated as NOS-associated diaphorase activity (NOSaD). Western blot analysis revealed immunoreactive bands for NOS-I-III in lysates from perinatal and adult muscle tissue and C2C12-myotubes that comigrated with prototypical proteins. In embryonic skeletal muscle, but not in adult myofibers, diffuse cytosolic staining and lack of sarcolemmal NOSaD activity and NOS-I immunoreaction were evident. In both myoblasts and fusioned myotubes, NOSaD and NOS isoforms I-III colocalize in the cytosol. Additionally, members of the sarcolemmal dystrophin-glycoprotein complex (i.e., dystrophin, adhalin, beta1-dystroglycan) immunolocalize in the cytosol of differentiating myoblasts, whereas anti-dystrophin and anti-beta1-dystroglycan clearly delineate the sarcolemma in myotubes. Thus, expression of NOS isoforms I-III and NOSaD is cytosolic in fusion-competent myoblasts during myotube formation in vitro. Interaction of NOSaD/NOS-I with the sarcolemmal dystrophin-complex known from mature myofibers is apparently lacking in prenatal muscle development and differentiating myoblasts. Localization of NOS isoforms thus characterized in myogenic cultures may help further to investigate regulated NO formation in muscle cells in vitro.
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PMID:Nitric oxide synthase (NOS) in mouse skeletal muscle development and differentiated myoblasts. 956 Apr 72

The response of rainbow trout (Oncorhynchus mykiss, Walbaum) towards probiotics present in the feed was investigated by examining the proteome of serum as a measure of the acute phase response (APR). Proteomic analysis by two-dimensional electrophoresis (2D) concurrently with mass spectrometry was used to detect APR related proteins in rainbow trout serum following feeding with probiotics Aeromonas sobria GC2 and Bacillus sp. JB-1. Three candidate proteins increased following use of GC2, and were putatively identified as NADH dehydrogenase, dystrophin and mKIAA0350. Conversely, one of the proteins, which were induced following use of JB-1 was identified as transferrin.
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PMID:Proteomic analysis of rainbow trout (Oncorhynchus mykiss, Walbaum) serum after administration of probiotics in diets. 1798 40

Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins.
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PMID:Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins. 2050 50

High intensity training induces muscle damage in dystrophin-deficient mdx mice, an animal model for Duchenne muscular dystrophy. However, low intensity training (LIT) rescues the mdx phenotype and even reduces the level of protein carbonylation, a marker of oxidative damage. Until now, beneficial effects of LIT were mainly assessed at the physiological level. We investigated the effects of LIT at the molecular level on 8-week-old wild-type and mdx muscle using 2D Western blot and protein-protein interaction analysis. We found that the fast isoforms of troponin T and myosin binding protein C as well as glycogen phosphorylase were overcarbonylated and downregulated in mdx muscle. Some of the mitochondrial enzymes of the citric acid cycle were overcarbonylated, whereas some proteins of the respiratory chain were downregulated. Of functional importance, ATP synthase was only partially assembled, as revealed by Blue Native PAGE analysis. LIT decreased the carbonylation level and increased the expression of fast isoforms of troponin T and of myosin binding protein C, and glycogen phosphorylase. In addition, it increased the expression of aconitate hydratase and NADH dehydrogenase, and fully restored the ATP synthase complex. Our study demonstrates that the benefits of LIT are associated with lowered oxidative damage as revealed by carbonylation and higher expression of proteins involved in energy metabolism and muscle contraction. Potentially, these results will help to design therapies for DMD based on exercise mimicking drugs.
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PMID:Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction. 2566 Sep 94