Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.8.1.4 (diaphorase)
 2,754 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Absence of nitric oxide synthase I despite the presence of the dystrophin complex in human striated muscle. 914 66

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.
 ...
PMID:Caveolin-3 and nitric oxide synthase I in healthy and diseased skeletal muscle. 954 84

Duchenne muscular dystrophy is the most commonly inherited neuromuscular disorder in humans. Although the primary genetic deficiency of dystrophin in X-linked muscular dystrophy is established, it is not well-known how pathophysiological events trigger the actual fibre degeneration. We have therefore performed a DIGE analysis of normal diaphragm muscle versus the severely affected x-linked muscular dystrophy (MDX) diaphragm, which represents an established animal model of dystrophinopathy. Out of 2398 detectable 2-D protein spots, 35 proteins showed a drastic differential expression pattern, with 21 proteins being decreased, including Fbxo11-protein, adenylate kinase, beta-haemoglobin and dihydrolipoamide dehydrogenase, and 14 proteins being increased, including cvHSP, aldehyde reductase, desmin, vimentin, chaperonin, cardiac and muscle myosin heavy chain. This suggests that lack of sarcolemmal integrity triggers a generally perturbed protein expression pattern in dystrophin-deficient fibres. However, the most significant finding was the dramatic increase in the small heat shock protein cvHSP, which was confirmed by 2-D immunoblotting. Confocal fluorescence microscopy revealed elevated levels of cvHSP in MDX fibres. An immunoblotting survey of other key heat shock proteins showed a differential expression pattern in MDX diaphragm. Stress response appears to be an important cellular mechanism in dystrophic muscle and may be exploitable as a new approach to counteract muscle degeneration.
 ...
PMID:Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP. 1683 51