The myokine decorin is regulated by contraction and involved in muscle hypertrophy

The health-promoting effects of regular exercise are well known, and myokines may mediate some of these effects. The small leucine-rich proteoglycan decorin has been described as a myokine for some time. However, its regulation and impact on skeletal muscle has not been investigated in detail. In this study, we report decorin to be differentially expressed and released in response to muscle contraction using different approaches. Decorin is released from contracting human myotubes, and circulating decorin levels are increased in response to acute resistance exercise in humans. Moreover, decorin expression in skeletal muscle is increased in humans and mice after chronic training. Because decorin directly binds myostatin, a potent inhibitor of muscle growth, we investigated a potential function of decorin in the regulation of skeletal muscle growth. In vivo overexpression of decorin in murine skeletal muscle promoted expression of the pro-myogenic factor Mighty, which is negatively regulated by myostatin. We also found Myod1 and follistatin to be increased in response to decorin overexpression. Moreover, muscle-specific ubiquitin ligases atrogin1 and MuRF1, which are involved in atrophic pathways, were reduced by decorin overexpression. In summary, our findings suggest that decorin secreted from myotubes in response to exercise is involved in the regulation of muscle hypertrophy and hence could play a role in exercise-related restructuring processes of skeletal muscle.     

Immunofluorescent subcellular localization of some muscle proteins: a comparison between tissue sections and isolated myofibrils.

The localization of parvalbumin in fish white muscle and of the calcium binding protein, of arginine kinase and of glycogen phosphorylase in crayfish tail muscle have been investigated by immunofluorescence using isolated myofibrils and muscle sections as starting materials. It is shown that the four proteins appear to be localized on the thin filaments when myofibrils are used as starting material. This result contrasts with previous observations where it appeared that parvalbumin in fish muscle and arginine kinase in crayfish muscle were distributed uniformly within the cell. This discrepancy is discussed in relation to the high solubility of these proteins. In the light of the present knowledge about striated muscles from these two organisms, it seems that the roles of parvalbumin in fish and of the calcium binding protein in crayfish are probably different.     

Muscle arm development in Caenorhabditis elegans

In several types of animals, muscle cells use membrane extensions to contact motor axons during development. To better understand the process of membrane extension in muscle cells, we investigated the development of Caenorhabditis elegans muscle arms, which extend to motor axons and form the postsynaptic element of the neuromuscular junction. We found that muscle arm development is a highly regulated process: the number of muscle arms extended by each muscle, the shape of the muscle arms and the path taken by the muscle arms to reach the motor axons are largely stereotypical. We also investigated the role of several cytoskeletal components and regulators during arm development, and found that tropomyosin (LEV-11), the actin depolymerizing activity of ADF/cofilin (UNC-60B) and, surprisingly, myosin heavy chain B (UNC-54) are each required for muscle arm extension. This is the first evidence that UNC-54, which is found in thick filaments of sarcomeres, can also play a role in membrane extension. The muscle arm phenotypes produced when these genes are mutated support a 'two-phase' model that distinguishes passive muscle arm development in embryogenesis from active muscle arm extension during larval development.     

A possible partitioning of segmental muscle stretch reflex into incompletely de-coupled parallel loops

Based on previous investigations on focussed signal transmission through the muscle stretch reflex system, a model is presented suggesting that different muscle areas (especially in large complex muscles such as the triceps surae muscle) may be regulated rather independently with respect to certain internal state variables, particularly internal length. Since the parallel localized reflex loops necessary for such local control tasks are inevitably coupled peripherally through the muscle and connective tissues, compensatory de-coupling elements would be required to reestablish at least partial independence. Whether and how this can be achieved at the level of spinal neuronal circuitry is investigated in connection with a discussion of the advantages of partially de-coupled reflex loops.     

Peroxisomes and peroxisomal functions in muscle. Studies with muscle cells from controls and a patient with the cerebro-hepato-renal (Zellweger) syndrome

In the present study we investigated peroxisomal functions in cultured human muscle cells from control subjects and from a patient with the Zellweger syndrome, a genetic disease characterized by the absence of morphologically distinguishable peroxisomes in liver and kidney. In homogenates of cultured muscle cells from control subjects, catalase is contained within subcellular particles, acyl-CoA:dihydroxyacetonephosphate acyltransferase activity is present and palmitoyl-CoA can be oxidized by a peroxisomal beta-oxidative pathway; these findings are indicative of the presence of peroxisomes in the cells. In homogenates of cultured muscle cells from the patient with the Zellweger syndrome, acyl-CoA:dihydroxyacetonephosphate acyltransferase activity was deficient, peroxisomal beta-oxidation of palmitoyl-CoA was impaired and catalase was not particle-bound. These findings indicate that functional peroxisomes are absent in muscle from patients with the Zellweger syndrome. We conclude that cultured human muscle cells can be used as a model system to study peroxisomal functions in muscle and the consequences for this tissue of a generalized dysfunction of peroxisomes.     

Dynamic properties of cat tenuissimus muscle

Some of the factors which influence the development of tension in cat tenuissimus muscle were studied quantitatively. Under isometric conditions, it was shown that the dynamic properties of the relationship between the tension of the muscle and its electrical stimulation depend on the mean rate of stimulation. This non-linear effect cannot be explained on the basis of the dependence of muscle tension on instantaneous rate of stimulation since the tension due to a stimulus following closely a previous stimulus is augmented, but the time course of the twitch response is unaltered. The interaction between the tension due to active contraction and that due to the viscoelastic properties of the muscle was investigated by independently varying muscle length and the rate of stimulation. Within the limits of resolution of the data, it was concluded that these two components of tension are additive and that muscle stiffness is related to the instantaneous tension of the muscle.     

Possible mechanisms of muscle cramp from temporal and spatial surface EMG characteristics.

In this study, the initiation and development of muscle cramp are investigated. For this, we used a 64-channel surface electromyogram (EMG) to study the triceps surae muscle during both cramp and maximal voluntary contraction (MVC) in four cramp-prone subjects and during cramp only in another four cramp-prone subjects. The results show that cramp presents itself as a contraction of a slowly moving fraction of muscle fibers, indicating that either the spatial arrangement of the motoneurons and muscle fibers is highly related or that cramp spreads at a level close to the muscle. Spectral analyses of the EMG and peak-triggered average potentials show the presence of extremely short potentials during cramp compared with during MVC. These results can also be interpreted in two ways. Either the motoneurons fire with enlarged synchronization during MVC compared with cramp, or smaller units than motor units are active, indicating that cramp is initiated close to or even at the muscle fiber level. Further research is needed to draw final conclusions.     

Origin and nature of correlations in the Ia feedback pathway of the muscle control system

Mammalian primary muscle spindle endings receive two inputs from fusimotor fibers and length changes of their extrafusal environment. Both inputs are also powerful noise sources disturbing the discharge patterns of the receptors. In this paper emphasis is laid on the extrafusal component. It is shown that extrafusal muscle activity can be viewed as a stochastic process which, acting as a common source, can correlate discharge patterns of adjacent muscle spindles. Some quantitative characteristics of these correlations and their relation to the underlying mechanical events are investigated in some detail in order to provide data for more theoretical considerations on their possible physiological importance.     

The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in muscles from vertebrates and invertebrates

1. The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in crude homogenates of vertebrate and invertebrate muscles are reported. 2. Pyruvate carboxylase activity was present in all insect flight muscles that were investigated: in homogenates of bumble-bee flight muscle the activity was inhibited by ADP and activated by acetyl-CoA, and it was distributed mainly in the mitochondrial fraction. This is the first demonstration of pyruvate carboxylase activity in muscle. However, the activity appears to be restricted to insect flight muscle, since it was not found in other invertebrate or vertebrate muscles. 3. Since the three enzymes were never found together in the same muscle, it is concluded that these enzymes cannot provide a pathway for the synthesis of glycogen from lactate or pyruvate in muscle. Other roles for these enzymes in muscle are suggested. In particular, pyruvate carboxylase may be present in insect flight muscle for the provision of oxaloacetate to support the large increase in activity of the tricarboxylic acid cycle which occurs when an insect takes flight.     

The influence of the way the muscle force is modeled on the predicted results obtained by solving indeterminate problems for a fast elbow flexion

A critical point in models of the human limbs when the aim is to investigate the motor control is the muscle model. More often the mechanical output of a muscle is considered as one musculotendon force that is a design variable in optimization tasks solved predominantly by static optimization. For dynamic conditions, the relationship between the developed force, the length and the contraction velocity of a muscle becomes important and rheological muscle models can be incorporated in the optimization tasks. Here the muscle activation can be a design variable as well. Recently a new muscle model was proposed. A muscle is considered as a mixture of motor units (MUs) with different peculiarities and the muscle force is calculated as a sum of the MUs twitches. The aim of the paper is to compare these three ways for presenting the muscle force. Fast elbow flexion is investigated using a planar model with five muscles. It is concluded that the rheological models are suitable for calculation of the current maximal muscle forces that can be used as weight factors in the objective functions. The model based on MUs has many advantages for precise investigations of motor control. Such muscle presentation can explain the muscle co-contraction and the role of the fast and the slow MUs. The relationship between the MUs activation and the mechanical output is more clear and closer to the reality.     

Fast and slow myosins as specific markers of muscle: an immunocytochemical study

Slow and fast myosins are specific markers of skeletal muscle. The specificity of anti-fast and anti-slow myosin antisera been verified on frozen and paraffin embedded tissues. The optimal fixative useful for routine histopathological purposes has been investigated. It is suggested that these two antisera can be used in the diagnosis of rhabdomyoblastic tumours substituting for or complementary to myoglobin, a well known marker of striated muscle.     

Coupled objective function to study the role of abdominal muscle forces in lifting using the kinematics-driven model

To circumvent the existing shortcoming of optimisation algorithms in trunk biomechanical models, both agonist and antagonist trunk muscle stresses to different powers are introduced in a novel objective function to evaluate the role of abdominal muscles in trunk stability and spine compression. This coupled objective function is introduced in our kinematics-driven finite element model to estimate muscle forces and to identify the role of abdominal muscles in upright standing while lifting symmetrically a weight at different heights. Predictive equations for the compression and buckling forces are developed. Results are also compared with the conventional objective function that neglects abdominal muscle forces. An overall optimal solution involving smaller spinal compression but higher trunk stability is automatically attained when choosing muscle stress powers at and around 3. Results highlight the internal oblique muscle as the most efficient abdominal muscle during the tasks investigated. The estimated relative forces in abdominal muscles are found to be in good agreement with the respective ratios of recorded electromyography activities.     

Enhanced stability of isolated muscles and actomyosin due to the action of anesthetics in subnarcotic concentrations

Subnarcotic concentrations of anesthetics and model anesthetics prolong the survival time of isolated living frog skeletal muscles, the time of contractile ability of the same glycerinated muscles, and the time of frog skeleton muscle actomyosin denaturation. The mode of anesthetic action involves hydrophobic interactions of anesthetics with the investigated biosystems. According to the quantitative analysis, physico-chemical parameters of the anesthetic-binding sites are identical in muscle and in muscle models. This result is interpreted as an evidence that anesthetic-evoked rising of contractile protein stability may be involved in the mechanism of stabilization of isolated muscles.     

Morphology of smooth muscle cells in the rat thoracic duct

Summary The three-dimensional cytoarchitecture and ultrastructure of the smooth muscle cells in the wall of the rat thoracic duct were investigated by scanning and transmission electron microscopy. The muscle layer basically consists of a single layer of circularly arranged cells. The smooth muscle cell is fusiform or ribbon-like in shape, as in veins or venules with a similar or smaller diameter. Connections by spinous processes are observed between adjacent muscle cells along their length. Spot-like membrane contacts frequently occur in areas where facing membranes are closely apposed. These are thought to be gap junctions and may be responsible for electrical coupling and mechanical attachment. Large invaginations arranged regularly in rows on the surface of the smooth muscle cells can be observed. These invaginations are closely associated with a flattened sarcoplasmic reticulum, and caveolae tend to open into the invaginations.     

Immunofluorescent subcellular localization of some muscle proteins: A comparison between tissue sections and isolated myofibrils

Summary The localization of parvalbumin in fish white muscle and of the calcium binding protein, of arginine kinase and of glycogen phosphorylase in crayfish tail muscle have been investigated by immunofluorescence using isolated myofibrils and muscle sections as starting materials.It is shown that the four proteins appear to be localized on the thin filaments when myofibrils are used as starting material. This result contrasts with previous observations where it appeared that parvalbumin in fish muscle and arginine kinase in crayfish muscle were distributed uniformly within the cell. This discrepancy is discussed in relation to the high solubility of these proteins.In the light of the present knowledge about striated muscles from these two organisms, it seems that the roles of parvalbumin in fish and of the calcium binding protein in crayfish are probably different.A preliminary report on this work was presented at the meeting of the Union of Swiss Societies for Experimental Biology, Zurich, 1977 (Benzonana et al., 1977a)     

Numbers of muscle nuclei and myosatellite cell nuclei in red and white axial muscle during growth of the carp (Cyprinus carpio)

We determined the percentages of muscle fibie nuclei and satellite nuclei over a growth range of carp ( Cyprinus carpio ), as the increase in the number of muscle fibre nuclei is an important aspect of the increase in muscle mass, and myosatellite cells are believed to be the source of new muscle fibre nuclei. In white as well as in red axial muscle the percentage of the nuclei present in muscle that are muscle nuclei (muscle fibre nuclei+myosatellite nuclei) remained constant during growth (54 and 32% respectively). The difference in the percentage of non-muscle nuclei between white and red axial muscle is mainly caused by the higher content of endothelial nuclei in red axial muscle.
In white axial muscle the DNA/protein ratio (nucleus/sarcoplasm ratio) decreased between 3 and 15 cm S.l. In red axial muscle we found a continuous decrease in DNA/protein ratio over the entire investigated size range (3–50 cm s.l.). This may be related to a longer occurrence of hyperplasia in red than in white axial muscle.
In both fibre types the percentage of muscle nuclei being myosatellite nuclei decreased with increasing length, In white axial muscle it decreased from about 5% in carp of 5 cm s.l. to less than 1% in carp of 20 cm S.L.; for red muscle these values were 11 and 3% respectively.
For white axial muscle we calculated that, especially in larger fish, the myosatellite ceils alone cannot account for the increase in the number of muscle fibre nuclei during growth. The percentage of proliferating nuclei in muscle tissue, measured by the uptake of 5-bromo-2'-deoxy-uridine, is high enough to account for the total increase in nuclei. So indirect evidence is available that another cell type present in the muscle tissue may also be involved in the formation of additional muscle fibre nuclei.     

Segregation and manifestations of the mtDNA tRNA(Lys) A-->G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.

We have studied the segregation and manifestations of the tRNA(Lys) A-->G(8344) mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA(Lys) mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrome had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that > 92% of mtDNA with the tRNA(Lys) mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA(Lys) mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. In two of the patients with MERRF syndrome, muscle specimens were obtained at different times. In both cases, biochemical measurements revealed a deteriorating respiratory-chain function, and in one case a progressive increase in the amount of cytochrome c oxidase-deficient muscle fibers was found.     

The properties of the extraocular muscles of the frog. II. Pharmacological properties of the isolated superior oblique and superior rectus muscles.

The pharmacological properties of the superior oblique and the superior rectus muscles of the frog's eye were investigated in comparison with those of a skeletal muscle (iliofibularis muscle) of the same animal. Acetylcholine causes sustained contractures of the extraocular muscles; this effect is increased by physostigmine and decreased or abolished by d-tubocurarine. Also the applications of succinylcholine, choline or caffeine are able to evoke contractures. There are no striking differences in pharmacological properties between extraocular and skeletal muscles of the frog. The time-course of the contractures and the sensitivity of the muscle preparations to the drugs which evoke contractures are identical in extraocular and iliofibularis muscles. In comparison with skeletal muscles there is no higher sensitivity of the extraocular muscles against curare-like drugs. The existence of adrenergic receptors could not be found neither in extraocular nor in skeletal muscles of the frog. It is concluded that in frogs no pharmacological differences exist between the muscle fibre types which compose the extraocular and the skeletal muscles.