calpain and Muscular-Diseases

Calpains are a family of Ca

Topics: Animals; Calpain; Enzyme Activation; Humans; Models, Biological; Muscle, Skeletal; Muscular Diseases; Organ Specificity

Calpains, a family of Ca(2+)-dependent cytosolic cysteine proteases, can modulate their substrates' structure and function through limited proteolytic activity. In the human genome, there are 15 calpain genes. The most-studied calpains, referred to as conventional calpains, are ubiquitous. While genetic studies in mice have improved our understanding about the conventional calpains' physiological functions, especially those essential for mammalian life as in embryogenesis, many reports have pointed to overactivated conventional calpains as an exacerbating factor in pathophysiological conditions such as cardiovascular diseases and muscular dystrophies. For treatment of these diseases, calpain inhibitors have always been considered as drug targets. Recent studies have introduced another aspect of calpains that calpain activity is required to protect the heart and skeletal muscle against stress. This review summarizes the functions and regulation of calpains, focusing on the relevance of calpains to cardiovascular disease.

Topics: Animals; Calpain; Cardiovascular Diseases; Enzyme Activation; Humans; Muscle, Skeletal; Muscular Diseases; Myocardium

Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies.

Topics: Adolescent; Adult; Calpain; Diagnostic Imaging; Dysferlin; Female; Humans; Magnetic Resonance Imaging; Male; Membrane Proteins; Muscle Proteins; Muscles; Muscular Diseases; Muscular Dystrophies, Limb-Girdle; Sarcoglycans; Tomography, X-Ray Computed; Ultrasonography

Topics: Animals; Calpain; Child; Diagnosis, Differential; Eosinophilia; Humans; Muscle Proteins; Muscular Diseases; Mutation; Myositis

Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres.

Topics: Animals; Calpain; Doxorubicin; Female; Heart; Mitochondria; Muscle, Skeletal; Muscular Diseases; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Topics: Animals; Calpain; Doxorubicin; Female; Mitochondria; Muscle, Skeletal; Muscular Diseases; Myocardium; Reactive Oxygen Species

In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified a previously reported homozygous mutation in the CAPN3 gene for an individual with an undiagnosed limb girdle muscular dystrophy, we evaluated ES as a generalizable clinical diagnostic tool by assessing the targeting efficiency and sequencing coverage of 88 genes associated with muscle disease (MD) and spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting each gene were defined using the UCSC and CCDS databases. The three exome-capture kits targeted 47-92% of bases within the UCSC-defined exons and 97-99% of bases within the CCDS-defined exons. An average of 61.2-99.5% and 19.1-99.5% of targeted bases per gene were sequenced to 20X coverage within the CCDS-defined MD and SPG coding exons, respectively. Greater than 95-99% of targeted known mutation positions were sequenced to ≥1X coverage and 55-87% to ≥20X coverage in every exome. We conclude, therefore, that ES is a rapid and efficient first-tier method to screen for mutations, particularly within the CCDS annotated exons, although its application requires disclosure of the extent of coverage for each targeted gene and supplementation with second-tier Sanger sequencing for full coverage.

Topics: Calpain; Exome; Female; Humans; Muscle Proteins; Muscular Diseases; Muscular Dystrophies, Limb-Girdle; Mutation; Paraplegia; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Young Adult

Camptocormia is a debilitating gait disorder characterized by the hyperflexion of the thoracolumbar spine during the upright position. Its etiologies are heterogenous, including parkinsonism and various neuromuscular disorders. Here, we report a camptocormia patient due to a late-onset axial myopathy with numerous lobulated fibers. The patient's father reportedly had similar symptoms. Myriad lobulated fibers are common among patients with an autosomal recessive muscular dystrophy due to calpain-3 gene (CAPN3) mutations or calpainopathy. CAPN3 sequencing revealed a single c.759-761delGAA mutation. Calpainopathy carriers are generally asymptomatic. The presence of lobulated fibers in this patient suggests that camptocormia could be a manifestation of calpainopathy carrier, although the possibility of a coexisting undiagnosed myopathy cannot be excluded. The current patient should spur the evaluation of camptocormia among calpainopathy carriers.

Topics: Aged; Biopsy; Calpain; Humans; Magnetic Resonance Imaging; Male; Muscle Fibers, Skeletal; Muscle Proteins; Muscular Atrophy, Spinal; Muscular Diseases; Muscular Dystrophies, Limb-Girdle; Mutation; Spinal Curvatures

MFM (myofibrillar myopathies) are caused by mutations in several sarcomeric components, including the Z-disc protein myotilin. The morphological changes typical of MFM include Z-disc alterations and aggregation of dense filamentous sarcomeric material. The causes and mechanisms of protein aggregation in myotilinopathies and other forms of MFM remain unknown, although impaired degradation may explain, in part, the abnormal protein accumulation. In the present paper we have studied the mechanisms regulating myotilin turnover, analysed the consequences of defective myotilin degradation and tested whether disease-causing myotilin mutations result in altered protein turnover. The results indicate that myotilin is a substrate for the Ca(2+)-dependent protease calpain and identify two calpain cleavage sites in myotilin by MS. We further show that myotilin is degraded by the proteasome system in transfected COS7 cells and in myotubes, and that disease-causing myotilinopathy mutations result in reduced degradation. Finally, we show that proteolysis-inhibitor-induced reduction in myotilin turnover results in formation of intracellular myotilin and actin-containing aggregates, which resemble those seen in diseased muscle cells. These findings identify for the first time biological differences between wt (wild-type) and mutant myotilin. The present study provides novel information on the pathways controlling myotilin turnover and on the molecular defects associated with MFM.

Topics: Animals; Calpain; Chlorocebus aethiops; Connectin; COS Cells; Cytoskeletal Proteins; Humans; Microfilament Proteins; Muscle Proteins; Muscular Diseases; Mutation; Myofibrils

Mechanical ventilation is known to induce ventilator-induced diaphragm dysfunction. Patients submitted to mechanical ventilation often receive massive doses of corticosteroids that may cause further deterioration of diaphragm function.. To examine whether the combination of 24 hours of controlled mechanical ventilation with corticosteroid administration would exacerbate ventilator-induced diaphragm dysfunction.. Rats were randomly assigned to a group submitted to 24 hours of controlled mechanical ventilation receiving an intramuscular injection of saline or 80 mg/kg methylprednisolone, a group submitted to 24 hours of spontaneous breathing receiving saline, or methylprednisolone and a control group.. The diaphragm force-frequency curve was shifted downward in the mechanical ventilation group, but this deleterious effect was prevented when corticosteroids were administered. Diaphragm cross-sectional area of type I fibers was similarly decreased in both mechanical ventilation groups while atrophy of type IIx/b fibers was attenuated after corticosteroid administration. The mechanical ventilation-induced reduction in diaphragm MyoD and myogenin protein expression was attenuated after corticosteroids. Plasma cytokine levels were unchanged while diaphragm lipid hydroperoxides were similarly increased in both mechanical ventilation groups. Diaphragmatic calpain activity was significantly increased in the mechanical ventilation group, but calpain activation was abated with corticosteroid administration. Inverse correlations were found between calpain activity and diaphragm force.. A single high dose of methylprednisolone combined with controlled mechanical ventilation protected diaphragm function from the deleterious effects of controlled mechanical ventilation. Inhibition of the calpain system is most likely the mechanism by which corticosteroids induce this protective effect.

Topics: Animals; Blotting, Western; Calpain; Diaphragm; Disease Models, Animal; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Gene Expression; Glucocorticoids; Injections, Intramuscular; Lipid Peroxidation; Male; Methylprednisolone; Muscle Contraction; Muscular Diseases; MyoD Protein; Myogenin; Rats; Rats, Wistar; Respiration, Artificial; Reverse Transcriptase Polymerase Chain Reaction; RNA; Treatment Outcome

Controlled mechanical ventilation (CMV) has been shown to result in elevated diaphragmatic proteolysis and atrophy together with diaphragmatic contractile dysfunction.. To test whether administration of leupeptin, an inhibitor of lysosomal proteases and calpain, concomitantly with 24 hours of CMV, would protect the diaphragm from the deleterious effects of mechanical ventilation.. Rats were assigned to either a control group or 24 hours of CMV; animals in the ventilation group received either a single intramuscular injection of saline or 15 mg/kg of the protease inhibitor, leupeptin.. Compared with control animals, mechanical ventilation resulted in a significant reduction of the in vitro diaphragm-specific force production at all stimulation frequencies. Leupeptin completely prevented this reduction in force generation. Atrophy of type IIx/b fibers was present after CMV, but not after treatment with leupeptin. Cathepsin B and calpain activities were significantly higher after CMV compared with the other groups; this was abolished by treatment with leupeptin. Significant inverse correlations were found between diaphragmatic force generation and cathepsin B and calpain activity, and illustrate the deleterious role of proteolysis in diminishing diaphragmatic force production after prolonged CMV.. Administration of the protease inhibitor leupeptin concomitantly with mechanical ventilation completely prevented ventilation-induced diaphragmatic contractile dysfunction and atrophy.

Topics: Animals; Blotting, Western; Calpain; Cathepsin B; Diaphragm; Disease Models, Animal; Fluorometry; Male; Mercaptopurine; Muscle Contraction; Muscular Diseases; Nucleic Acid Synthesis Inhibitors; Rats; Rats, Wistar; Respiration, Artificial; Treatment Outcome

To clarify the involvement of calpains in sarcolemmal remodeling, we examined the expression of calpains and their substrate, alpha-fodrin, in various disorders of muscle. Although immunohistological reactions for alpha-fodrin and calpains were weak in normal control muscles, intense immunoreactivity for alpha-fodrin at the sarcolemma and for calpains throughout the cytoplasm were detected in small muscle fibers from patients with inflammatory myositis (IM), rhabdomyolysis (Rhab), and Duchenne muscular dystrophy (DMD). Most of the calpain-alpha-fodrin double-positive muscle fibers in IM and Rhab also expressed the developmental form of myosin heavy chain. The sarcolemma of these small muscle fibers reacted with an antibody that specifically recognizes the 150-kDa fragments of alpha-fodrin (SBDP 150s) cleaved by calpain, but not caspase 3. Western blot analysis confirmed these results. These observations indicate that calpain is activated and reacts with alpha-fodrin as a substrate at the sarcolemma, and plays a key role in modulating sarcolemmal proteins to adapt to the specific conditions in each myopathy.

Topics: Adult; Aged; Antibody Specificity; Calpain; Carrier Proteins; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Male; Microfilament Proteins; Middle Aged; Muscle, Skeletal; Muscular Diseases; Muscular Dystrophy, Duchenne; Myosin Heavy Chains; Myositis; Peptide Fragments; Rhabdomyolysis; Sarcolemma

Topics: Actin Cytoskeleton; Arm; Calpain; Creatine Kinase; Creatine Kinase, MM Form; Humans; In Situ Nick-End Labeling; Isoenzymes; Male; Middle Aged; Muscle Proteins; Muscle Weakness; Muscular Atrophy; Muscular Diseases; Myosins; Remission, Spontaneous

To clarify the mechanism of muscle fiber destruction in sarcoid myopathy, muscle biopsy specimens were examined from patients with sarcoid myopathy, polymyositis, or dermatomyositis. In sarcoid myopathy, noncaseating granulomatous lesions were located in the perimysium or endomysium or both. Little fiber atrophy, caused by mechanical compression of the granuloma, was seen, and there was no evidence of ischemia-induced changes (i.e., perifascicular atrophy) due to microangiopathy in muscles. Immunoreactivity for membrane-associated cytoskeletal proteins such as dystrophin and merosin was detected homogeneously along the surface of many small granulomas in intrafascicular lesions. These granulomas showed a characteristic phenotypic cellular distribution: CD68(+) and CD4(+) cells were present in the center, and some CD8(+) cells were found at the periphery, indicating typical sarcoid granuloma formation in each muscle fiber. Strong expression of proteases such as cathepsin B, calpain II and ubiquitin-proteasome was observed in macrophages and epithelioid cells but not in lymphocytes in granulomas within muscle fibers or those in the endomysium or perimysium. The expression intensity was stronger in premature-stage granulomas than in late-stage granulomas. Weak expression of these proteases was detected mainly in some muscle fibers invaded by epithelioid cells and macrophages and in a few atrophic or necrotic fibers adjacent to inflammatory foci but not in fibers of fascicles without granuloma formation or in fibers in perifascicular areas. Our results suggest that muscle fiber destruction in sarcoid myopathy is caused mainly by direct invasion of granulomatous inflammatory cells into muscle fibers during the process of granuloma formation rather than by mechanical compression or ischemia. Furthermore, the proteases derived from epithelioid cells and macrophages may play an important role in muscle fiber destruction.

Topics: Adult; Aged; Calpain; Cathepsin B; Cysteine Endopeptidases; Female; Histocytochemistry; Humans; Immunohistochemistry; Male; Middle Aged; Multienzyme Complexes; Muscle, Skeletal; Muscular Diseases; Proteasome Endopeptidase Complex; Sarcoidosis; Ubiquitin

A defect of the gene for p94 (calpain 3), a skeletal muscle-specific calpain, is responsible for limb girdle muscular dystrophy type 2A (LGMD2A), or 'calpainopathy', which is an autosomal recessive and progressive neuromuscular disorder. To study the relationships between the physiological functions of p94 and the etiology of LGMD2A, we created transgenic mice that express an inactive mutant of p94, in which the active site Cys129 is replaced by Ser (p94:C129S). Three lines of transgenic mice expressing p94:C129S mRNA at various levels showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wild-type mice of the same age had almost none. There was more p94 protein produced in aged transgenic mice muscles and it showed significantly less autolytic degradation activity than that of wild-type mice. Although no necrotic-regenerative fibers were observed, the age and p94:C129S expression dependence of the phenotypes strongly suggest that accumulation of p94:C129S protein causes these myopathy phenotypes. The p94:C129S transgenic mice could provide us with crucial information on the molecular mech-anism of LGMD2A.

Topics: Animals; Binding Sites; Body Weight; Calpain; Connectin; Cysteine; Female; Immunohistochemistry; Mice; Mice, Transgenic; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Muscular Dystrophies; Mutation; Phenotype; Plasmids; Polymerase Chain Reaction; Protein Kinases; Serine

Dysferlin is the protein product of the gene (DYSF) that is defective in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy. Calpain 3 is the muscle-specific member of the calcium activated neutral protease family and primary mutations in the CAPN3 gene cause limb girdle muscular dystrophy type 2A. The functions of both proteins remain speculative. Here we report a secondary reduction in calpain 3 expression in eight out of 16 patients with a primary dysferlinopathy and clinical features characteristic of limb girdle muscular dystrophy type 2B or Miyoshi myopathy. Previously CAPN3 analysis had been undertaken in three of these patients and two showed seemingly innocuous missense mutations, changing calpain 3 amino acids to those present in the sequences of calpains 1 and 2. These results suggest that there may be an association between dysferlin and calpain 3, and further analysis of both genes may elucidate a novel functional interaction. In addition, an association was found between prominent expression of smaller forms of the 80 kDa fragment of laminin alpha 2 chain (merosin) and dysferlin-deficiency.

Topics: Calpain; DNA Mutational Analysis; Dysferlin; Humans; Membrane Proteins; Muscle Proteins; Muscular Diseases; Muscular Dystrophies

The calpain proteolytic system was examined in the longissimus muscle (LD) of heterozygote pigs carrying a single copy of a mutation in the skeletal muscle ryanodine receptor gene (RyR1) that is associated with porcine stress syndrome and reduced meat quality. Conventional British White-type pigs (n = 30) were selected from a commercial line on the basis of slaughter weight, backfat depth, and pH at 45 min postmortem > 6.0; based on DNA analysis, 11 were heterozygous RyR1 mutants (Nn), and 19 were normal genotype (NN). The LD samples were taken from carcasses at 2, 4, and 24 h postmortem for calpain analysis with enzyme assay and immunoblotting, using specific antisera raised against recombinant polypeptides derived from calpain large subunits and calpastatin. Shear force (SF) was measured after conditioning for 8 d at 2 degrees C and did not differ between Nn and NN groups. The extractable activity of mu-calpain decreased over 24 h postmortem (P < .001), with no significant difference in activity between NN and Nn animals at any time. The activity of m-calpain also decreased with time (P < .001), but it was lower at all times in Nn than in normal genotypes (P < .001). After Western blotting, the immunoreactivity of mu- and m-calpain large subunit bands declined over 24 h postmortem (P < .001); values for mu-calpain were higher (P < .05) and for m-calpain were lower (P < .001) in heterozygotes than in normal animals at each sampling time. The calpastatin antibody detected a major band of 135 kDa that declined with time postmortem but did not differ between Nn and NN genotypes at any sampling time. These data indicate that the levels of extractable mu- and m-calpain, but not calpastatin, may be different in pigs that carry the RyR1 mutation.

Topics: Animals; Calpain; Genotype; Heterozygote; Meat; Molecular Weight; Muscle, Skeletal; Muscular Diseases; Mutation; Ryanodine Receptor Calcium Release Channel; Swine

In a previous report we suggested that muscle fibers in distal myopathy with rimmed vacuoles (DMRV) were degraded by both lysosomal proteolysis (cathepsins) and Ca2+-dependent, nonlysosomal proteolysis (calpain). Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, we examined the role of the ATP-ubiquitin-dependent proteolytic pathway (proteasomes) in myofiber degradation in this myopathy. Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak. Quantitative analysis showed more reactivity for proteasomes in DMRV muscles and, to a lesser extent, in muscles from muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis patients. In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers. Ubiquitin accumulation was marked within rimmed vacuoles and was seen less extensively in the cytoplasm of atrophic fibers. The latter proteins colocalized well. In other diseased muscles, proteasomes and ubiquitin showed a positive reaction in the atrophic or necrotic fibers. The results indicate increased proteasome and ubiquitin in these muscle fibers as well as in other diseased muscle fibers. We suggest that the ATP-ubiquitin-proteasome proteolytic pathway as well as the nonlysosomal calpain and the lysosomal proteolytic pathway may participate in the muscle fiber degradation in DMRV.

Topics: Adenosine Triphosphate; Adult; Biopsy; Calpain; Cysteine Endopeptidases; Female; Humans; Lysosomes; Male; Middle Aged; Multienzyme Complexes; Muscle Fibers, Skeletal; Muscle Proteins; Muscular Atrophy; Muscular Diseases; Phagocytosis; Proteasome Endopeptidase Complex; Ubiquitins; Vacuoles

Immunocytochemical analysis of muscle specimens from 5 patients with acute quadriplegic myopathy indictes that depletion of either fast or slow myosin occurs in this disorder. The initial lesion consists of focal myosin loss in nonatrophic fibers. Other structural proteins (actin, titin, nebulin) are spared or affected only at an advanced stage of the disease. Attempts at regeneration, evidenced by expression of fetal myosin and desmin, occur in some fibers. Calpain expression is markedly enhanced in the affected fibers, implicating an altered calcium homeostasis in the evolution of the pathologic process. By contrast, cathepsin B and ubiquitin expressions are only minimally affected. The history of 1 of our patients indicates that severe systemic illness in and of itself can cause acute quadriplegic myopathy.

Topics: Acute Disease; Adult; Aged; Animals; Calpain; Chick Embryo; Electrophysiology; Female; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Myosins; Peptide Hydrolases; Quadriplegia

Late-onset distal myopathy showed numerous rimmed vacuoles with the same properties as autophagic vacuoles. Electron microscopy showed numerous degenerated mitochondria, glycogen, or cell membranes in rimmed vacuoles, but no evidence that these vacuoles engulfed and contained intact or partially disrupted myofibrils. Immunostaining for myosin, alpha-actinin, and actin, however, was sometimes positive within the vacuoles. Compared to the control muscle, there was increased staining activity by calpain around the rimmed vacuoles or in the cytoplasm of mainly atrophic fibers. The result seems to indicate an increase of calpain activity in these muscle fibers. We hypothesize that the myofibrils as well as mitochondria, glycogen, or cell membranes in this myopathy are degraded finally through a lysosomal autophagic process. However, the breakdown of the myofibrils may be not initiated by lysosomal activation; rather it may be the result of extralysosomal processes such as the calpain system.

Topics: Actinin; Actins; Adult; Calpain; Cathepsin B; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Endopeptidases; Female; Humans; Immunohistochemistry; Lysosomes; Male; Middle Aged; Mitochondria; Muscles; Muscular Diseases; Myofibrils; Myosins; Vacuoles

1. This study was initiated to ascertain the possibility of biochemically monitoring the rhabdomyonecrosis that occurs after organophosphate poisoning. The evolution of different parameters has been assessed in the rat 6, 16, 24 and 48 h following 0.67 x LD50 of soman. 2. Acetylcholinesterase (AChE) was inhibited to 60% of the control value in the diaphragm at 6 and 16 h and serum ChE levels inhibited to an average of 30% of the control value. At 24 h, total blood, brain and diaphragm AChE were inhibited by 40, 69 and 38%, respectively. 3. Rhabdomyonecrosis lesions occurred in the diaphragm after 24 h and were accompanied by a concurrent increase in urinary creatine excretion rate (300% of the control) and serum total creatine phosphokinase activity (280% of the control). Calcium-activated neutral protease and phosphorylase a activities were elevated in the muscle at the same time. 4. These biochemical markers will prove useful for investigating the possible relationships between the different neuromuscular syndromes occurring in the course of an OP poisoning and potential therapeutic or protective pharmacological measures.

Topics: Acetylcholinesterase; Animals; Behavior, Animal; Biomarkers; Brain; Calpain; Creatine; Creatine Kinase; Female; Muscular Diseases; Necrosis; Organophosphate Poisoning; Phosphorylase a; Rats; Rats, Sprague-Dawley; Respiratory Muscles; Soman

Topics: Animals; Calpain; Cell Membrane; Cell Survival; Humans; Isoenzymes; Molecular Structure; Muscular Diseases

Topics: Aminoquinolines; Animals; Calpain; Injections, Intramuscular; Lysosomes; Muscular Diseases; Necrosis; Protein Denaturation; Rats; Rats, Inbred Strains