Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Calpains (calcium-activated cysteine proteinases) have evolved by gene fusion events involving calmodulin-like genes, cysteine proteinase genes and other sequences of unknown origin. 2. The enzymes are composed of two non-identical subunits, each of which contains functional calcium-binding sequences. 3. Calpains are inhibited by the endogenous protein inhibitor, calpastatin and some calmodulin antagonists are also inhibitors of calpain. A number of synthetic proteinase inhibitors also inhibit calpains. 4. Calpains can be activated by phospholipids, an endogenous protein activator and some amino acid derivatives. 5. Various protein substrates for calpains have been recognized in vitro, but the identity of in situ substrates remains unclear. 6. Proposals have been made for calpain function, including involvement in signal transduction, platelet activation, cell fusion, mitosis and cytoskeleton and contractile protein turnover. 7. Calpain and calpastatin expression is altered in a number of abnormal states including muscular dystrophy, muscle denervation and tenotomy, hypertension and platelet abnormalities.
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PMID:Calpains (intracellular calcium-activated cysteine proteinases): structure-activity relationships and involvement in normal and abnormal cellular metabolism. 227 16

Long-term administration of the beta 2-adrenergic agonist clenbuterol in mdx mice was used to test the hypothesis that increasing contractile protein content in skeletal muscle will decrease the progression of muscular dystrophy. C57BL/10SNJ (control) and dystrophic (mdx) mice were given clenbuterol (1.0-1.5 mg/kg body weight/day) in the drinking water. Ventilatory function and morphological and functional characteristics of soleus (SOL) and diaphragm (DIA) muscles were evaluated. Clenbuterol administration was associated with increased SOL muscle weight, and SOL muscle weight to body weight ratio in control and mdx mice at both ages. There was a 22% increase in myosin concentration of mdx DIA at 1 year of age, correlating well with increased normalized active tension in mdx DIA at this age. Also, absolute tetanic tension increased in control and mdx SOL with clenbuterol at both ages. Ventilatory function was significantly impaired in mdx mice at both ages and clenbuterol administration did not alleviate this. Clenbuterol treatment was associated with a 30-40% increase in fatigability in DIA and SOL muscles of control and mdx mice at both ages. Furthermore, 1-year-old mdx mice receiving clenbuterol exhibited deformities in hindlimbs and spine. These results suggest that long-term clenbuterol treatment has a positive effect on muscle growth and force generation, but has adverse side effects such as increased muscle fatigability and development of deformities.
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PMID:Beneficial versus adverse effects of long-term use of clenbuterol in mdx mice. 747 69

The cardiomyocyte membrane cytoskeleton consists of the costameric proteins that mediate force transduction from the cell to the extracellular matrix, and a sub-membrane network composed of dystrophin and associated proteins. Studies of the precise cellular distribution of dystrophin and of the consequences of genetic mutations leading to abnormal expression of the dystrophin molecule, as occurs in Duchenne and Becker's muscular dystrophies, highlight potential functional roles of this sub-membrane protein complex in cardiomyocytes. Detailed investigation of dystrophin distribution using the complementary cell imaging techniques of immunoconfocal microscopy and freeze-fracture cytochemistry at the electron-microscopical level show that, in contrast to rat cardiomyocytes, the dystrophin network in human cardiomyocytes is locally enriched at costameres. Thus located, the dystrophin network appears to have a mechanical role, involving stabilization of the peripheral plasma membrane during the repetitive distortion associated with cardiac contraction and, in the human myocyte, contributing to lateral force-transduction. Evidence from animal models of muscular dystrophy and from investigation of the interactions of the sub-membrane cytoskeleton with other membrane-associated proteins including ion channels, receptors and enzymes, further suggests a role for dystrophin in organization and regulation of membrane domains. The relative preservation of the membrane cytoskeleton in non-dystrophic dilated cardiomyopathy and in ischemic cardiomyopathy, conditions in which the myocyte contractile apparatus and internal desmin-based cytoskeleton are commonly disrupted, emphasizes the vital role of the membrane cytoskeleton in cell survival. Continued cardiomyocyte survival despite loss of contractile protein organization has implications in the potential for reversibility of left ventricular remodeling that can be achieved in the clinical setting.
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PMID:Dystrophin and the cardiomyocyte membrane cytoskeleton in the healthy and failing heart. 1622 6