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At least 325 records · Page 18

Responses of amino acids in hindlimb muscles to recovery from hypogravity and unloading by tail-cast suspension

Amino acids were assayed in muscles from rats exposed to 7 days of hypogravity and 12 h of gravity (F) or 6 days of suspension with (R) or without (H) 12 h of loading. In these groups, lower aspartate was common only to the soleus (SOL) relative to control muscles, the smallest difference being in group R. This difference in aspartate for F and H, but not for R, correlated with lower malate suggesting diminution of citric acid cycle intermediates. The R SOL value was increased over the H SOL. Therefore desite 12 h of loading, the F SOL was more comparable to the H SOL. The role of stress in preventing recovery of the F SOL was apparent from the ratios of glutamine/glutamate. Synthesis of glutamine is enhanced by glucocorticoids and is reflected by an increased ratio. In 5 of the 6 F muscles studied, this ratio was greater than in controls. In contrast, the ratio in all R muscles was similar to controls and showed recovery from the values in H muscles. Hence the post-flight treatment of F rats may have produced additional stress. Despite this stress, in some respects the SOL responses to hypogravity were similar to its responses to unloding by suspension.

Tischler, M. E.↗

Muscle protein and glycogen responses to recovery from hypogravity and unloading by tail-cast suspension

Previous studies in this laboratory using the tail-bast hindlimb suspension model have shown that there are specific changes in protein and carbohydrate metabolism in the soleus muscle due to unloading. For example, 6 days of unloading caused a 27 percent decrease in mass and a 60 percent increse in glycogen content in the soleus muscle, while the extensor digitorum longus muscle was unaffected. Also, fresh tissue tyrosine and its in vitro release from the muscle are increased in the unloaded soleus, indicating that this condition causes a more negative protein balance. With these results in mind, studies to investigate the effect of hypogravity on protein and carbohydrate metabolism in a number of rat hindlimb muscles were carried out.

Henriksen, E. J.↗

Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles

Muscle atrophy in humans can occur during prolonged bed rest, plaster cast immobilization, and space flight. In the present study, the suspension model used by Musacchia et al. (1983) is employed to investigate changes in protein synthesis and degradation in fast-twitch phasic (extensor digitorum longus) and slow-twitch postural (soleus) muscles in the rat, following hypokinesia and hypodynamia. In addition, the use of passive stretch was examined as a means of preventing atrophy. The obtained results suggest that the mechanisms controlling the processes of protein synthesis and protein breakdown during muscle disuse atrophy may be independent of each other. It appears, however, that the muscle atrophy due to hypokinesia and hypodynamia can be temporarily prevented by passively stretching a muscle.

Loughna, P.↗

A possible role for endogenous glucocorticoids in orchiectomy-induced atrophy of the rat levator ani muscle - Studies with RU 38486, a potent and selective antiglucocorticoid

RU38486, a potent and selective antiglucocorticoid, was employed to study a possible role for endogenous glucocorticoids in atrophy of the levator ani muscle secondary to castration of male rats. RU38486 was shown to block (3H) triamcinolone acetonide binding to cytosol from levator ani muscle. Daily oral administration of RU38486 to castrated rats partially prevented atrophy of the levator ani muscle, as well as a decrease in RNA concentration. In a control group receiving RU38486 alone, the levator ani underwent significant 20 percent hypertrophy. Administration of exogenous dexamethasone also caused pronounced atrophy of the levator ani muscle. This atrophy was prevented, to a significant degree, by simultaneous oral administration of Ru38486. It is concluded that endogenous glucocorticoids, the actions of which are blocked by RU38486, may be involved in regulation of the mass of the levator ani muscle in intact rats.

Konagaya, Masaaki↗

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

Tsika, R. W.↗

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Tsika, R. W.↗

Control of abdominal and expiratory intercostal muscle activity during vomiting - Role of ventral respiratory group expiratory neurons

The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal muscle activity during vomiting was investigated in cats. Two series of experiments were performed: in one, the activity of VRG E neurons was recorded during fictive vomiting in cats that were decerebrated, paralyzed, and artificially ventilated; in the second, the abdominal muscle activity during vomiting was compared before and after sectioning the axons of descending VRG E neurons in decerebrate spontaneously breathing cats. The results show that about two-thirds of VRG E neurons that project at least as far caudally as the lower thoracic cord contribute to internal intercostal muscle activity during vomiting. The remaining VRG E neurons contribute to abdominal muscle activation. As shown by severing the axons of the VRG E neurons, other, as yet unidenified, inputs (either descending from the brain stem or arising from spinal reflexes) can also produce abdominal muscle activation.

Miller, Alan D.↗

Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity

The effects of simulated microgravity (30 days of continuous 6-deg headdown bedrest, BR) on the structural and metabolic characteristics of human skeletal muscle were determined. Percutaneous needle biopsy samples obtained from the vastus lateralis and soleus muscles before and after the headdown BR were analyzed for histochemical, biochemical and ultrastructual changes. It was found that headdown BR led to decreases in both fast-twitch and slow-twitch fiber areas in both muscles, and there was evidence of remodeling of the ultrastructure in both muscles. The activities of beta-hydroxyacyl-CoA dehydrogenase and citrate synthase were reduced during BR, but phosphofructokinase and lactate dehydrogenase activities did not change. The results indicate that 30-d exposure to simulated microgravity decreased the capacity for aerobic energy supply of human skeletal muscle and led to a disorganization of the contractile machinery.

Hikida, Robert S.↗

Experiment K-6-07. Metabolic and morphologic properties of muscle fibers after spaceflight

The present study demonstrates that the general capability of skeletal muscle to maintain its proteins decreases rapidly in response to space flight. The present findings suggest further that the magnitude of enzymatic and cell volumes changes in response to space flight depend on several factors including the muscle and its fiber type composition. It appears that in order to associate physiological relevance to the observed enzymatic changes, cell volume should be considered also. Although it remains unclear as to the stimulus, or lack of stimulus, that triggers the rapid changes in muscle proteins in response to space flight, ground-based models of muscle atrophy suggest that the reduction in mechanical loading of muscle may be more important than the total amount of activation over a 24-hr period.

Edgerton, R.↗

Effects of oxygen deprivation on incubated rat soleus muscle

Isolated soleus muscle deprived of oxygen produces more lactate and alanine than oxygen-supplied muscle. Oxygenated muscle synthesized glutamine, while anoxic muscle used this amino acid. Oxygen deprivation decreased adenine nucleotides leading to the efflux of nucleosides. Protein synthesis and degradation responded differently to anoxia. Synthesis almost completely ceased, while proteolysis increased. Therefore, protein degradation in soleus muscle is enhanced when energy supplies and oxygen tension are low.

Fagan, Julie M.↗

Quantitation and immunocytochemical localization of ubiquitin conjugates within rat red and white skeletal muscles

Solid-phase immunochemical methods were employed to probe the dynamics of ubiquitin pools within selected rat skeletal muscles. The total ubiquitin content of red muscles was greater than that of white muscles, even though the fractional conjugation was similar for both types of muscles. The specificity for conjugated ubiquitin in solid-phase applications, previously demonstrated for an affinity-purified antibody against SDS-denatured ubiquitin, was retained when used as a probe for ubiquitin-protein adducts in tissue sections. Immunohistochemical localization revealed that differences in ubiquitin pools derived from the relative content of red (oxidative) vs white (glycolytic) fibers, with the former exhibiting a higher content of ubiquitin conjugates. Subsequent immunogold labeling demonstrated statistically significant enhanced localization of ubiquitin conjugates to the Z-lines in both red and white muscle fiber types.

Riley, Danny A.↗

A unique problem of muscle adaptation from weightlessness: The deceleration deficiency

Decelerator problems of the knee are emphasized since the lower leg musculature is known to atrophy in response to weightlessness. However, other important decelerator functions are served by the shoulder muscles, in particular the rotator cuff muscles. Problems in these muscles often result in tears and dislocations as seen in baseball pitchers. It is noteworthy that at least one device currently exists that can measure concentric and eccentric muscle loading including a submaximal simulated free weight exercise (i.e., force-controlled) and simultaneously record integrated EMG analysis appropriate for assessment of all muscle functional activities. Studies should be undertaken to provide information as to the performance of maximal and submaximal exercise in space travelers to define potential problems and provide rationale for prevention.

Stauber, William T.↗

Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats

The effects of a 7-day spaceflight (SF), 7- and 14-day-long whole body suspension (WBS), and 7-day-long recovery on the muscle weight and the morphology of the soleus and the extensor digitorum longus (EDL) of rats were investigated. It was found that the effect of 7-day-long SF and WBS were highly comparable for both the soleus and the EDL, although the soleus muscle from SF rats showed greater cross-sectional area reduction than that from WBS rats. With a longer duration of WBS, there was a continued reduction in cross-sectional fast-twitch fiber area. Muscle plasticity, in terms of fiber and capillary responses, showed differences in responses of the two types of muscles, indicating that antigravity posture muscles are highly susceptible to unloading.

Musacchia, X. J.↗

Skeletal muscle responses to lower limb suspension in humans

The morphological responses of human skeletal muscle to unweighting were assessed by analyzing multiple transaxial magnetic resonance (MR) images of both lower limbs and skeletal muscle biopsies of the unweighted lower limb before and after six weeks of unilaterial (left) lower limb suspension (ULLS). Results indicated that, as a results of 6 weeks of unweighting (by the subjects walking on crutches using only one limb), the cross sectional area (CSA) of the thigh muscle of the unweighted left limb decreased 12 percent, while the CSA of the right thigh muscle did not change. The decrease was due to a twofold greater response of the knee extensors than the knee flexors. The pre- and post-ULLS biopsies of the left vastus lateralis showed a 14 percent decrease in average fiber CSA due to unweighting. The number of capillaries surrounding the different fiber types was unchanged after ULLS. Results showed that the adaptive responses of human skeletal muscle to unweighting are qualitatively, but not quantitatively, similar to those of lower mammals and not necessarily dependent on the fiber-type composition.

Hather, Bruce M.↗

Muscle strength and endurance following lowerlimb suspension in man

The effect of lower-limb suspension on the muscle strength and muscle endurance was investigated in six men subjected to four weeks of unilateral unloading of a lower limb (using of a harness attached to a modified shoe), followed by seven weeks of weight-bearing recovery. Results showed a decrease in the cross-sectional area (CSA) of the thigh muscle and in the average peak torque (APT) during three bouts of 30 concentric knee extensions. While the the thigh muscle CSA returned to normal after seven weeks of recovery, the APT recovery was still reduced by 11 percent, suggesting that muscle metabolic function was severely affected by unloading and was not restored by ambulation.

Tesch, Per A.↗

Crustaceans as a model for microgravity-induced muscle atrophy

Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein meatabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca2(+) -dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

Mykles, D. L.↗

Interactive effects of growth hormone and exercise on muscle mass in suspended rats

Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

Grindeland, Richard E.↗

Adaptations of human skeletal muscle fibers to spaceflight

Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities, and cross-sectional area (CSA) as found in rat, cat, and other species. One difference seems to be that fast fibers with high mitochrondrial content occur less frequently in humans than in the rat or cat. Recently, we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type, and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number, and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiologica consequences of the muscle adaptations that occur in humans in response to spaceflight.

M. Kathleen Day↗