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Muscle Degeneration (muscle + degeneration)
Selected AbstractsRedox regulation of skeletal muscleIUBMB LIFE, Issue 8 2008Malcolm J. Jackson Abstract The potential deleterious roles of "oxidative stress" have been studied in skeletal muscle for over 30 years, but recent studies have identified that reactive oxygen species and nitric oxide generated by skeletal muscle can exert regulatory roles in cell signalling processes. This "redox regulation" appears to depend upon the reversible oxidation of cysteine residues within key proteins with reversible gluathionylation and formation of protein disulphides potentially leading to changes in the activities of proteins such as enzymes, transcription factors or transporters. Control of this process is dependent upon the local redox environment pertaining at a subcellular level. This short review provides examples of redox-regulated physiological processes in skeletal muscle that include some activation of transcription factors and changes in gene expression that result from contractile activity and the modulation of force generation during sustained contractions. There is also increasing evidence that dysregulation of redox-sensitive processes plays a role in the loss of muscle mass and function that occurs during normal ageing and in the gross muscle degeneration in disorders such as the muscular dystrophies. © 2008 IUBMB IUBMB Life, 60(8): 497,501, 2008 [source] Vaccine-associated granulomatous inflammation and melanin accumulation in Atlantic salmon, Salmo salar L., white muscleJOURNAL OF FISH DISEASES, Issue 1 2005E O Koppang Abstract The purpose of this study was to investigate the nature of variably sized pigmented foci encountered in fillets of farmed Atlantic salmon, Salmo salar L. The material was sampled on the fillet production line and on salmon farms from fish with an average size of 3 kg from various producers. The fish had been routinely vaccinated by injection. Gross pathology, histology, immunohistochemistry using antisera against major histocompatibility complex (MHC) class II , chain and transmission electron microscopy (TEM) were used to characterize the changes. Macroscopically, melanized foci were seen penetrating from the peritoneum deep into the abdominal wall, sometimes right through to the skin, and also embedded in the caudal musculature. Histological investigation revealed muscle degeneration and necrosis, fibrosis and granulomatous inflammation containing varying numbers of melano-macrophages. Vacuoles, either empty or containing heterogeneous material, were frequently seen. The presence of abundant MHC class II+ cells indicated an active inflammatory condition. TEM showed large extracellular vacuoles and leucocytes containing homogeneous material of lipid-like appearance. The results showed that the melanized foci in Atlantic salmon fillet resulted from an inflammatory condition probably induced by vaccination. The described condition is not known in wild salmon and in farmed salmon where injection vaccination is not applied. [source] Hyposialylation of neprilysin possibly affects its expression and enzymatic activity in hereditary inclusion-body myopathy muscleJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Aldobrando Broccolini Abstract Autosomal recessive hereditary inclusion-body myopathy (h-IBM) is caused by mutations of the UDP- N -acetylglucosamine 2-epimerase/N -acetylmannosamine kinase gene, a rate-limiting enzyme in the sialic acid metabolic pathway. Previous studies have demonstrated an abnormal sialylation of glycoproteins in h-IBM. h-IBM muscle shows the abnormal accumulation of proteins including amyloid-, (A,). Neprilysin (NEP), a metallopeptidase that cleaves A,, is characterized by the presence of several N-glycosylation sites, and changes in these sugar moieties affect its stability and enzymatic activity. In the present study, we found that NEP is hyposialylated and its expression and enzymatic activity reduced in all h-IBM muscles analyzed. In vitro, the experimental removal of sialic acid by Vibrio Cholerae neuraminidase in cultured myotubes resulted in reduced expression of NEP. This was most likely because of a post-translational modification consisting in an abnormal sialylation of the protein that leads to its reduced stability. Moreover, treatment with Vibrio Cholerae neuraminidase was associated with an increased immunoreactivity for A, mainly in the form of distinct cytoplasmic foci within myotubes. We hypothesize that, in h-IBM muscle, hyposialylated NEP has a role in hampering the cellular A, clearing system, thus contributing to its abnormal accumulation within vulnerable fibers and possibly promoting muscle degeneration. [source] Gene therapy flexes muscleTHE JOURNAL OF GENE MEDICINE, Issue 9 2005A European Society of Gene Therapy commentary on progress in gene therapy for Duchenne muscular dystrophy, amyotrophic lateral sclerosis Abstract This commentary highlights the promising results of recent studies in animal models of Duchenne muscular dystrophy and amyotrophic lateral sclerosis that have clearly demonstrated the potential of gene therapy for tackling these diseases. In the absence of effective drugs or other treatments, these advances in gene therapy technology represent the best hope for those patients and families that are blighted by these diseases. Background Diseases characterized by progressive muscle degeneration are often incurable and affect a relatively large number of individuals. The progressive deterioration of muscle function is like the sword of Damocles that constantly reminds patients suffering from these diseases of their tragic fate, since most of them will eventually die from cardiac or pulmonary dysfunction. Some of these disorders are due to mutations in genes that directly influence the integrity of muscle fibers, such as in Duchenne muscular dystrophy (DMD), a recessive X-linked genetic disease. Others result from a progressive neurodegeneration of the motoneurons that are essential for maintaining muscle function, such as in amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig's disease. The genetic basis of DMD is relatively well understood as it is due to mutations in the dystrophin gene that encodes the cognate sarcolemmal protein. In contrast, the cause of ALS is poorly defined, with the exception of some dominantly inherited familial cases of ALS that are due to gain-of-function mutations in the gene encoding superoxide dismutase (SODG93A). Gene therapy for these disorders has been hampered by the inability to achieve widespread gene transfer. Moreover, since familial ALS is due to a dominant gain-of-function mutation, inhibition of gene expression (rather than gene augmentation) would be required to correct the phenotype, which is particularly challenging. Copyright © 2005 John Wiley & Sons, Ltd. [source] T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse,THE JOURNAL OF PATHOLOGY, Issue 2 2007A Farini Abstract Abnormal connective tissue proliferation following muscle degeneration is a major pathological feature of Duchenne muscular dystrophy (DMD), a genetic myopathy due to lack of the sarcolemmal dystrophin protein. Since this fibrotic proliferation is likely to be a major obstacle to the efficacy of future therapies, research is needed to understand and prevent the fibrotic process in order to develop an effective treatment. Murine muscular dystrophy (mdx) is genetically homologous to DMD, and histopatological alterations are comparable to those of the muscles of patients with DMD. To investigate the development of fibrosis, we bred the mdx mouse with the scid immunodepressed mouse and analysed fibrosis histologically; we used ELISA analysis to determine TGF-,1 expression. Significant reduction of fibrosis and TGF-,1 expression was found in the muscles of the scid/mdx mice. However, we observed similar centrally located nuclei, necrosis, muscle degeneration and muscle force compared to the mdx animals. These data demonstrate a correlation between the absence of B and T lymphocytes and loss of fibrosis accompanied by reduction of TGF-,1, suggesting the importance of modulation of the immune system in DMD. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenitaACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010C. Kornblum Kornblum C, Lutterbey GG, Czermin B, Reimann J, von Kleist-Retzow J-C, Jurkat-Rott K, Wattjes MP. Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita. Acta Neurol Scand: 2010: 121: 131,135. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background,,, Muscle magnetic resonance imaging (MRI) is the most sensitive method in the detection of dystrophic and non-dystrophic abnormalities within striated muscles. We hypothesized that in severe myotonia congenita type Becker muscle stiffness, prolonged transient weakness and muscle hypertrophy might finally result in morphologic skeletal muscle alterations reflected by MRI signal changes. Aim of the study,,, To assess dystrophic and/or non-dystrophic alterations such as fatty or connective tissue replacement and muscle edema in patients with severe recessive myotonia congenita. Methods,,, We studied three seriously affected patients with myotonia congenita type Becker using multisequence whole-body high-field MRI. All patients had molecular genetic testing of the muscle chloride channel gene (CLCN1). Results,,, Molecular genetic analyses demonstrated recessive CLCN1 mutations in all patients. Two related patients were compound heterozygous for two novel CLCN1 mutations, Q160H and L657P. None of the patients showed skeletal muscle signal changes indicative of fatty muscle degeneration or edema. Two patients showed muscle bulk hypertrophy of thighs and calves in line with the clinical appearance. Conclusions,,, We conclude that (i) chloride channel dysfunction alone does not result in skeletal muscle morphologic changes even in advanced stages of myotonia congenita, and (ii) MRI skeletal muscle alterations in myotonic dystrophy must be clear consequences of the dystrophic disease process. [source] | |||||||||||||