Skeletal muscle metabolism in hypokinetic rats
Amino acid metabolism in hypokinesia is discussed. The effects of passive stretching of muscles in hypokinesia are considered.
Tischler, M. E.↗
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Alterations in mitochondria and sarcoplasmic reticulum from heart and skeletal muscle of horizontally casted primates
Horizontally body-casted rhesus monkeys are used as an animal model in order to study the physiological changes known as cardiovascular deconditioning which occur during weightless conditions. No difference was found between the experimental and control animals in heart mitochondrial oxidative phosphorylation which indicates that no apparent changes occurred in the primary energy-producing system of the heart. A marked increase in cytochrome oxidase activity was observed in the casted primate heart mitochondria compared to controls, while a 25% decrease in respiratory substrate-supported calcium uptake was found in casted primate heart mitochondria compared to controls. Sacroplasmic reticulum isolated from the primate hearts revealed marked changes in calcium transport activities. It is concluded that the marked depression in cardiac sarcoplasmic reticulum functions indicates altered calcium homeostasis in the casted-primate heart which could be a factor in cardiovascular deconditioning.
Sordahl, L. A.↗
Effect of denervation and reinnervation on oxidation of 6-(C-14) glucose by rat skeletal muscle homogenates
The effects of denervation and reinnervation of the rat extensor digitorum longus muscle on the oxidation of 6-(C-14) glucose to (C-14)O2 is investigated. Results show that the rate of (C-14)O2 production decreased dramatically following denervation and the decrease became significant 20 days after nerve section. The changes which occurred prior to day 20 apparently reflected the decline of muscle mass. The decreased (C-14)O2 production was found to be due to reduced capacity of the enzymatic system, while there was no change in the apparent affinity for glucose. Results of mixing experiments showed that the loss of oxidative capacity following denervation is not caused by the production of soluble inhibitors by degenerating muscle. Measurements of the (C-14)O2 revealed that oxidative metabolism recovered during reinnervation. The specific activity in reinnervated muscles displayed an 'overshoot' of approximately 50 percent, which returned to control levels by day 60. The time-course of the denervation-mediated change indicates that altered oxidative capacity is secondary to events that initiate dennervation changes in muscle, although diminished oxidative capacity may be of considerable metabolic significance in denervated muscle.
Dubois, D. C.↗
Research on the adaptation of skeletal muscle to hypogravity Past and future directions
The results of previous research on the cellular effects of microgravity on rat tissue are reviewed and areas of future necessary research are identified. The rats were flown on board Cosmos 605, 782, and 936. Postflight tissue analyses revealed increases in connective tissue cells and focal disruption of muscle fibers due to the microgravity environment of space. Evidence has been found for muscular and neural changes occurring as a result of reentry stresses. It is suggested that a data base be established for quantizing muscle function with electromyography, measurements of force output, and length measurement. The data can serve as a reference for comparisons with data obtained in orbiting laboratories such as the Spacelab. The experiments will have a goal of defining and preventing the mechanism of neuromuscular atrophy.
Riley, D. A.↗
Biochemical and histochemical adaptations of skeletal muscle to rat suspension
The influence of rat suspension on soleus disuse and atrophy was investigated to measure changes in fiber area and number and to determine if suspension elicited changes in lysosomal protease activity and rate of calcium uptake by the sarcoplasmic reticulum. The infuence of rat suspension on myosin light chain phosphorylation and succinate dehydrogenase activity are determined.
Templeton, G. H.↗
Skeletal muscle metabolism in hypokinetic rats
Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.
Tischler, M. E.↗
Alterations in skeletal muscle with disuse atrophy
Progress is reported in the following areas: (1) microgel electrophoresis identification of single fibers; (2) skinned fiber preparation; and (3) microbiochemical techniques for assaying important enzymes and substrates in single fibers.
Fitts, R. H.↗
Acid phosphatase and protease activities in immobilized rat skeletal muscles
The effect of hind-limb immobilization on selected Iysosomal enzyme activities was studied in rat hing-limb muscles composed primarily of type 1. 2A, or 2B fibers. Following immobilization, acid protease and acid phosphatase both exhibited signifcant increases in their activity per unit weight in all three fiber types. Acid phosphatase activity increased at day 14 of immobilization in the three muscles and returned to control levels by day 21. Acid protease activity also changed biphasically, displaying a higher and earlier rise than acid phosphatase. The pattern of change in acid protease, but not acid phosphatase, closely parallels observed muscle wasting. The present data therefore demonstrate enhanced proteolytic capacity of all three fiber types early during muscular atrophy. In addition, the data suggest a dependence of basal hydrolytic and proteolytic activities and their adaptive response to immobilization on muscle fiber composition.
Witzmann, F. A.↗
Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse
Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.
Gupta, R. C.↗
Responses of skeletal muscle to unloading, a review
Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.
Tischler, M. E.↗
Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization
The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.
Fitts, R. H.↗
Effects of suspension hypokinesia/hypodynamia on rat skeletal muscle
The effects of suspension hypokinesia/hypodynamia (H/H) on properties of soleus and plantaris muscles of rats were studied. The objective was to compare the effects of this model to those of disuse atrophy. After 12 d of H/H, there were significant decreases in soleus and plantaris muscle wet weight and citrate synthase activity. Soleus muscle was affected to a greater extent than plantaris muscle. There was a significant decrease in noncollagen protein content of H/H soleus muscle. Triceps brachii muscles did not display significant changes in any parameters measured, suggesting that observed changes were not due to systemic factors. There was no significant change in the water content of H/H soleus or plantaris muscles. Suspension H/H causes muscle changes different from those secondary to limb immobilization, in which soleus and plantaris muscles are equally affected.
Max, S. R.↗
Fibre-type specificity and effect of thyroid hormone on glucose 6-phosphate dehydrogenase activity in normal and denervated skeletal muscles of the rat
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Max, S. R.↗
Responses of skeletal muscle to unloading - A review
Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.
Tischler, M. E.↗
Changes in skeletal muscle properties following hindlimb suspension
Changes in AChE regulation, the functions of the sarcoplasmic reticulum (SR), and muscle fiber-type population in the extensor digitorium longus (EDL) and soleus of male rats suspended in a nonweight-bearing position are studied. Muscle weight, AChE activity, protein content, SR calcium loading rates, and muscle types in the suspended and control rats are evaluated and compared. It is observed that following 1-4 weeks of suspension the EDL is unaffected; however, the soleus muscle weight, and protein content decrease and the AChE activity increases. The SR calcium loading rates of EDL decrease 10 percent and the soleus increase 50 percent in the suspended rats. The data reveal that the population of muscle type 1 (slow fibers) decreases and type 2 (fast fibers) increases for the soleus, and the distribution is unchanged for the EDL of the suspended rats. It is detected that a nonweight-bearing position affects the soleus (a fast-twitch muscle), but not the EDL (a slow-twitch muscle).
Patterson, G. T.↗
Reduction-oxidation state and protein degradation in skeletal muscles of growing rats
The relationship between the NAD redox state and protein degradation during growth was studied in isolated soleus and extensor digitorum longus muscles of 4- to 14-week-old rats. As muscle size increased with age, protein breakdown slowed and the muscles became progressively more reduced as shown by higher ratios of lactate/pyruvate in incubated and fresh-frozen muscle. Correlations were strong between redox state of protein degradation, and muscle mass, and between redox state and protein degradation. This relationship may be important in the slowing of muscle breakdown that occurs with age.
Fagan, Julie M.↗
Reduction-oxidation state and protein degradation in skeletal muscle of fasted and refed rats
Redox state and protein degradation were measured in isolated muscles of fasted (up to 10 d) and refed (up to 4 d) 7- to 14-wk-old rats. Protein degradation in the extensor digitorum longus muscle, but not in the soleus muscle, was greater in the fasted rats than in weight-matched muscle from fed rats. The NAD couple was more oxidized in incubated and fresh extensor digitorum longus muscles and in some incubated soleus muscles of fasted rats than in weight-matched muscle from fed rats. In the extensor digitorum longus muscle of refed or prolonged fasted rats, protein degradation was slower and the NAD couple was more reduced than in the fed state. Therefore, oxidation of the NAD couple was associated with increased muscle breakdown during fasting, whereas reduction of the NAD couple was associated with muscle conservation and deposition.
Fagan, Julie M.↗
Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro
The regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture is studied. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.
Max, Stephen R.↗