Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat soleus muscles were overloaded with intent to induce a relative increase in fast fibres and modifications in muscular stiffness. The overloading technique was a training period consisting of an 11-week vertical jump programme. The method of controlled releases was used to obtain tension/extension curves characterizing the elastic behaviour of the soleus. Fibre typing was made by myofibrillar adenosine 5'-triphosphatase staining. With regard to a control group, training resulted in a relative decrease in type I fibres for the benefit of type II fibres. Training also induced a decrease in muscle stiffness as attested notably by significant differences in maximal extension. These results are interpreted in terms of modifications occurring in the active fraction of the so-called series elastic component.
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PMID:Stiffness changes and fibre type transitions in rat soleus muscle produced by jumping training. 196 82

Isolated skinned frog skeletal muscle fibers were activated (increasing [Ca2+]) and then relaxed (decreasing [Ca2+]) with solution changes, and muscle force and stiffness were recorded during the steady state. To investigate the actomyosin cycle, the biochemical species were changed (lowering [MgATP] and elevating [H2PO4-]) to populate different states in the actomyosin ATPase cycle. In solutions with 200 microM [MgATP], compared with physiological [MgATP], the slope of the plot of relative steady state muscle force vs. stiffness was decreased. At low [MgATP], cross-bridge dissociation from actin should be reduced, increasing the population of the last cross-bridge state before dissociation. These data imply that the last cross-bridge state before dissociation could be an attached low-force-producing or non-force-producing state. In solutions with 10 mM total Pi, compared to normal levels of MgATP, the maximally activated muscle force was reduced more than muscle stiffness, and the slope of the plot of relative steady state muscle force vs. stiffness was reduced. Assuming that in elevated Pi, Pi release from the cross-bridge is reversed, the state(s) before Pi release would be populated. These data are consistent with the conclusion that the cross-bridges are strongly bound to actin before Pi release. In addition, if Ca2+ activates the ATPase by allowing for the strong attachment of the myosin to actin in an A.M.ADP.Pi state, it could do so before Pi release. The calcium sensitivity of muscle force and stiffness in solutions with 4 mM [MgATP] was bracketed by that measured in solutions with 200 microM [MgATP], where muscle force and stiffness were more sensitive to calcium, and 10 mM total Pi, where muscle force and stiffness were less sensitive to calcium. The changes in calcium sensitivity were explained using a model in which force-producing and rigor cross-bridges can affect Ca2+ binding or promote the attachment of other cross-bridges to alter calcium sensitivity.
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PMID:Muscle force and stiffness during activation and relaxation. Implications for the actomyosin ATPase. 296 85

Soleus muscle atrophy was induced by hind-limb suspension of rats for 3 weeks with the intention of inducing a relative increase in the percentage of fast-twitch fibres and assessing modifications in muscle stiffness. A method of dual controlled releases was used to obtain tension/extension curves and force/velocity relationships characterizing the mechanical behaviour of the soleus. Fibre typing was achieved by myofibrillar adenosine 5'-triphosphatase staining. Results showed that hindlimb suspension decreased the percentage of slow-twitch fibres (-31%) to the profit of fast-twitch fibres (+370%) and intermediate fibres (+255%). This led to an increase in maximal shortening velocity. Tension/extension curves indicated a decrease in soleus stiffness after 3 weeks of unloading. Changes in elastic properties are interpreted in terms of modifications occurring in the active part and the passive part of the so-called series elastic component. These changes also suggest that the parameters derived from a twitch are inappropriate to account for modifications in speed-related properties of muscle.
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PMID:Changes in stiffness induced by hindlimb suspension in rat soleus muscle. 776 Dec 57

31-P MR spectroscopy has been used to investigate metabolic events surrounding muscular contraction in a patient with an unusual myopathy characterized by clinical signs of muscle stiffness and swelling after prolonged exercise. Histological assays demonstrated a predominance of type II fibers with tubular aggregates. These structures had low calcium content although calcium-ATPase protein was present. Metabolic measurements were normal at rest except for the presence of a marked signal in the phosphodiester region which could reflect membrane abnormalities. Exercise-induced PCr consumption was in the normal range but the extent of the related intracellular acidosis was abnormally large. Kinetics of PCr and PCr/Pi ratio post-exercise recovery were delayed, but were likely to reflect the effect of the very low end-of-exercise pH rather than an aerobic deficiency. Finally, proton efflux from muscle to bloodstream, measured during the initial recovery period, was delayed, indicating altered mechanisms of proton handling. The most prominent metabolic abnormality recorded is the large glycogenolysis-induced pH decrease which might be linked to either abnormal activation of glycogenolysis and/or impaired proton and lactate handling within the muscle. The association between tubular aggregates and hyperacidosis is of interest but the exact causal relationship remains to be elucidated.
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PMID:Magnetic resonance spectroscopy and histological study of tubular aggregates in a familial myopathy. 883 87

The active and passive contractile performance of skeletal muscle fibers largely depends on the myosin heavy chain (MHC) isoform and the stiffness of the titin spring, respectively. Open questions concern the relationship between titin-based stiffness and active contractile parameters, and titin's importance for total passive muscle stiffness. Here, a large set of adult rabbit muscles (n = 37) was studied for titin size diversity, passive mechanical properties, and possible correlations with the fiber/MHC composition. Titin isoform analyses showed sizes between approximately 3300 and 3700 kD; 31 muscles contained a single isoform, six muscles coexpressed two isoforms, including the psoas, where individual fibers expressed similar isoform ratios of 30:70 (3.4:3.3 MD). Gel electrophoresis and Western blotting of two other giant muscle proteins, nebulin and obscurin, demonstrated muscle type-dependent size differences of < or =70 kD. Single fiber and single myofibril mechanics performed on a subset of muscles showed inverse relationships between titin size and titin-borne tension. Force measurements on muscle strips suggested that titin-based stiffness is not correlated with total passive stiffness, which is largely determined also by extramyofibrillar structures, particularly collagen. Some muscles have low titin-based stiffness but high total passive stiffness, whereas the opposite is true for other muscles. Plots of titin size versus percentage of fiber type or MHC isoform (I-IIB-IIA-IID) determined by myofibrillar ATPase staining and gel electrophoresis revealed modest correlations with the type I fiber and MHC-I proportions. No relationships were found with the proportions of the different type II fiber/MHC-II subtypes. Titin-based stiffness decreased with the slow fiber/MHC percentage, whereas neither extramyofibrillar nor total passive stiffness depended on the fiber/MHC composition. In conclusion, a low correlation exists between the active and passive mechanical properties of skeletal muscle fibers. Slow muscles usually express long titin(s), predominantly fast muscles can express either short or long titin(s), giving rise to low titin-based stiffness in slow muscles and highly variable stiffness in fast muscles. Titin contributes substantially to total passive stiffness, but this contribution varies greatly among muscles.
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PMID:Isoform diversity of giant proteins in relation to passive and active contractile properties of rabbit skeletal muscles. 1623 Apr 67

Aging affects many motor functions, notably the spinal stretch reflexes and muscle spindle sensitivity. Spindle activation also depends on the elastic properties of the structures linked to the proprioceptive receptors. We have calculated a spindle efficacy index, SEI, for old rats. This index relates the spindle sensitivity, deduced from electroneurograms recording (ENG), to the passive stiffness of the muscle. Spindle sensitivity and passive incremental stiffness were calculated during ramp and hold stretches imposed on pseudo-isolated soleus muscles of control rats (aged 4 months, n=12) and old rats (aged 24 months, n=16). SEI were calculated for the dynamic and static phases of ramp (1-80 mm/s) and for hold (0.5-2mm) stretches imposed at two reference lengths: length threshold for spindle afferents discharges, L(n) (neurogram length) and slack length, L(s). The passive incremental stiffness was calculated from the peak and steady values of passive tension, measured under the stretch conditions used for the ENG recordings, and taking into account the muscle cross-sectional area. The pseudo-isolated soleus muscles were also stretched to establish the stress-strain relationship and to calculate muscle stiffness constant. The contralateral muscle was used to count muscle spindles and spindle fibers (ATPase staining) and immunostained to identify MyHC isoforms. L(n) and L(s) lengths were not significantly different in the control group, while L(n) was significantly greater than L(s) in old muscles. Under dynamic conditions, the SEI of old muscles was the same as in controls at L(s), but it was significantly lower than in controls at L(n) due to increased passive incremental stiffness under the stretch conditions used to analyze the ENG. Under static conditions, the SEI of old muscles was significantly lower than control values at all the stretch amplitudes and threshold lengths tested, due to increased passive incremental stiffness and decreased spindle sensitivity at L(s). The muscle stiffness constant values were greater in old muscles than in controls, confirming the changes in elastic properties under passive conditions due to aging. Aging also altered the intrafusal fibers: it increased the mean number of intrafusal fibers and the contents in the slow, neonatal and developmental isoforms intrafusal of MyHC have been modified. These structural modifications do not seem great enough to counteract the loss of the spindle sensitivity or the spindle efficacy under passive conditions and after the nerve was severed. However, they may help to maintain the spindle afferent message under natural conditions and under fusimotor control.
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PMID:Aging affects passive stiffness and spindle function of the rat soleus muscle. 1711 2

A Dutch Improved Red and White cross-breed heifer calf was evaluated for a muscular disorder resulting in exercise induced muscle stiffness. Clinical findings included generalized exercise-induced muscle spasms with normal response to muscle percussion. Electromyography showed no myotonic discharges, thus ruling out myotonia. Whereas histological examination of muscle tissue was unremarkable, Ca(2+)-ATPase activity of sarcoplasmatic reticulum membranes (SERCA1) was markedly decreased compared to control animals. Mutation analysis revealed the presence of a missense mutation in the ATP2A1 gene encoding the SERCA1 protein (p.Arg559Cys). The present case presents similarities to human Brody's disease, but also to pseudomyotonia and congenital muscular dystonia previously described in different cattle breeds.
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PMID:Pseudomyotonia, a muscle function disorder associated with an inherited ATP2A1 (SERCA1) defect in a Dutch Improved Red and White cross-breed calf. 2054 55

Brody disease is a rare inherited myopathy due to reduced sarcoplasmic reticulum Ca(2+) ATPase (SERCA)1 activity caused by mutations in ATP2A1, which causes delayed muscle relaxation and silent cramps. So far the disease has mostly been diagnosed by measurement of SERCA1 activity. Since mutation analysis became more widely available, it has appeared that not all patients with reduced SERCA1 activity indeed have ATP2A1 mutations, and a distinction between Brody disease (with ATP2A1 mutations) and Brody syndrome (without ATP2A1 mutations) was proposed. We aim to compare the clinical features of patients with Brody disease and those with Brody syndrome and detect clinical features which help to distinguish between the two. In addition, we describe the Brody syndrome phenotype in more detail. We therefore performed a literature review on clinical features of both Brody disease and Brody syndrome and a cross-sectional clinical study consisting of questionnaires, physical examination, and a review of medical files in 17 Brody syndrome patients in our centre. The results showed that Brody disease presents with an onset in the 1st decade, a generalized pattern of muscle stiffness, delayed muscle relaxation after repetitive contraction on physical examination, and autosomal recessive inheritance. Patients with Brody syndrome more often report myalgia and experience a considerable impact on daily life. Future research should focus on the possible mechanisms of reduction of SERCA activity in Brody syndrome and other genetic causes, and on evaluation of treatment options.
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PMID:Brody syndrome: a clinically heterogeneous entity distinct from Brody disease: a review of literature and a cross-sectional clinical study in 17 patients. 2270 59

Mitsugumin 53 (MG53) is a member of the membrane repair system in skeletal muscle. However, the roles of MG53 in the unique functions of skeletal muscle have not been addressed, although it is known that MG53 is expressed only in skeletal and cardiac muscle. In the present study, MG53-binding proteins were examined along with proteins that mediate skeletal muscle contraction and relaxation using the binding assays of various MG53 domains and quadrupole time-of-flight mass spectrometry. MG53 binds to sarcoplasmic reticulum Ca(2+)-ATPase 1a (SERCA1a) via its tripartite motif (TRIM) and PRY domains. The binding was confirmed in rabbit skeletal muscle and mouse primary skeletal myotubes by co-immunoprecipitation and immunocytochemistry. MG53 knockdown in mouse primary skeletal myotubes increased Ca(2+)-uptake through SERCA1a (more than 35%) at micromolar Ca(2+) but not at nanomolar Ca(2+), suggesting that MG53 attenuates SERCA1a activity possibly during skeletal muscle contraction or relaxation but not during the resting state of skeletal muscle. Therefore MG53 could be a new candidate for the diagnosis and treatment of patients with Brody syndrome, which is not related to the mutations in the gene coding for SERCA1a, but still accompanies exercise-induced muscle stiffness and delayed muscle relaxation due to a reduction in SERCA1a activity.
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PMID:Mitsugumin 53 attenuates the activity of sarcoplasmic reticulum Ca(2+)-ATPase 1a (SERCA1a) in skeletal muscle. 2310 43

Brody disease was first described as a benign pseudo-myotonic disorder with muscular stiffness, which increased with exercise. Biochemical and genetic studies have pointed out its close relationship to a functional defect of the fast-twitch sarcoplasmic reticulum Ca(++) ATPase pump (SERCA1) encoded by the ATP2A1 gene located on chromosome 16. The histopathological features in this form of myopathy were generally described as non-specific, i.e. moderate degree of type 2 fibre atrophy and excess of internal nuclei. We here present the clinical and histopathological features of a patient with Brody disease over a 19-year follow-up period. This patient had two heterozygous ATP2A1 mutations and complained about muscle stiffness immediately after effort. He had suffered from this since early childhood and exhibited clinical symptoms mimicking myotonia. Histological, ultrastructural and cytogenetic analyses revealed morphologically abnormal nuclei with polyploidy. In this report, we discuss the possible links between the consequences of the genetic abnormality and the peculiar aspect of the nuclei.
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PMID:Atypical nuclear abnormalities in a patient with Brody disease. 2624 58


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