Tetanic contractions impair sarcomeric Z-disk of atrophic soleus muscle via calpain pathway

The aim of this study was to determine whether or not over-activation of calpains during running exercise or tetanic contractions was a major factor to induce sarcomere lesions in atrophic soleus muscle. Relationship between the degrees of desmin degradation and sarcomere lesions was also elucidated. We observed ultrastructural changes in soleus muscle fibers after 4-week unloading with or without running exercise. Calpain activity and desmin degradation were measured in atrophic soleus muscles before or after repeated tetani in vitro. Calpain-1 activity was progressively increased and desmin degradation was correspondingly elevated in 1-, 2-, and 4-week of unloaded soleus muscles. Calpain-1 activity and desmin degradation had an additional increase in unloaded soleus muscles after repeated tetani in vitro. PD150606, an inhibitor of calpains, reduced calpain activity and desmin degradation during tetanic contractions in unloaded soleus muscles. The 4-week unloading decreased the width of myofibrils and Z-disk in soleus fibers. After running exercise in unloaded group, Z-disks of adjacent myofibrils were not well in register but instead were longitudinally displaced. Calpain inhibition compromised exercise-induced misalignment of the Z-disks in atrophic soleus muscle. These results suggest that tetanic contractions induce an over-activation of calpains which lead to higher degrees of desmin degradation in unloaded soleus muscle. Desmin degradation may loose connections between adjacent myofibrils, whereas running exercise results in sarcomere injury in unloaded soleus muscle.     

Enzyme activities and reduced insulin need with training in streptozotocin-induced diabetic rats

Following a 12-week endurance training program, the SDH activities of gastrocnemius medialis muscle of streptozotocin-induced diabetic animals increased by 50%. On the other hand, a 14% decrease was observed in the same muscle of diabetic animals submitted to power training. No difference between groups, for soleus and gastrocnemius lateralis muscles following the two different training regimens was observed. It can be concluded that streptozotocin-induced diabetic animals controlled by daily insulin demonstrate a normal muscle enzyme adaptation to exercise. These data also demonstrate that regular power and/or endurance exercise can result in reduced exogenous insulin need in streptozotocin-induced diabetic rats (18% and 28% respectively), suggesting a more efficient membrane transport of glucose with induced exercise, and a decreased need for insulin supported transport.     

Effects of a shoulder injury prevention strength training program on eccentric external rotator muscle strength and glenohumeral joint imbalance in female overhead activity athletes

Imbalance of the eccentrically-activated external rotator cuff muscles versus the concentrically-activated internal rotator cuff muscles is a primary risk factor for glenohumeral joint injuries in overhead activity athletes. Nonisokinetic dynamometer based strength training studies, however, have focused exclusively on resulting concentric instead of applicable eccentric strength gains of the external rotator cuff muscles. Furthermore, previous strength training studies did not result in a reduction in glenoumeral joint muscle imbalance, thereby suggesting that currently used shoulder strength training programs do not effectively reduce the risk of shoulder injury to the overhead activity athlete. Two collegiate women tennis teams, consisting of 12 women, participated in this study throughout their preseason training. One team (n = 6) participated in a 5-week, 4 times a week, external shoulder rotator muscle strength training program next to their preseason tennis training. The other team (n = 6) participated in a comparable preseason tennis training program, but did not conduct any upper body strength training. Effects of this strength training program were evaluated by comparing pre- and posttraining data of 5 maximal eccentric external immediately followed by concentric internal contractions on a Kin-Com isokinetic dynamometer (Chattecx Corp., Hixson, Tennessee). Overall, the shoulder strength training program significantly increased eccentric external total work without significant effects on concentric internal total work, concentric internal mean peak force, or eccentric external mean peak force. In conclusion, by increasing the eccentric external total exercise capacity without a subsequent increase in the concentric internal total exercise capacity, this strength training program potentially decreases shoulder rotator muscle imbalances and the risk for shoulder injuries to overhead activity athletes.     

Exercise training increases oxidative capacity and attenuates exercise-induced ultrastructural damage in skeletal muscle of aged horses.

Exercise training improves functional capacity in aged individuals. Whether such training reduces the severity of exercise-induced muscle damage is unknown. The purpose of the present study was to determine the effect of 10 wk of treadmill exercise training on skeletal muscle oxidative capacity and exercise-induced ultrastructural damage in six aged female Quarter horses (>23 yr of age). The magnitude of ultrastructural muscle damage induced by an incremental exercise test before and after training was determined by electron microscopic examination of samples of triceps, semimembranosus, and masseter (control) muscles. Maximal aerobic capacity increased 22% after 10 wk of exercise training. The percentage of type IIa myosin heavy chain increased in semimembranosus muscle, whereas the percentage of type IIx myosin heavy chain decreased in triceps muscle. After training, triceps muscle showed significant increases in activities of both citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase. Attenuation of exercise-induced ultrastructural muscle damage occurred in the semimembranosus muscle at both the same absolute and the same relative workloads after the 10-wk conditioning period. We conclude that aged horses adapt readily to intense aerobic exercise training with improvements in endurance, whole body aerobic capacity, and muscle oxidative capacity, and heightened resistance to exercise-induced ultrastructural muscle cell damage. However, adaptations may be muscle-group specific.     

Novel myosin isoform in nuclear chain fibers of rat muscle spindles produced in response to endurance swimming.

With the use of myosin adenosinetriphosphatase (ATPase) and immunofluorescence staining methods, the adaptive responses of intrafusal and extrafusal fibers to endurance swimming were studied in frozen sections of rat soleus (SOL) and extensor digitorum longus (EDL) muscles. Glycogen depletion confirmed muscle fatigue at the end of a standardized bout of exercise. No significant age-dependent changes in myosin isoforms were detected in any fibers. The 12-wk training increased type I fibers by 10.9% in the SOL and type IIa fibers in the EDL by 16.6%. In trained muscle sections, both staining methods identified a permuted chain fiber, expressed the same as the myosin isoform in the bag2 fiber. However, no exercise-induced change of myosin isoform profile was found in the bag1 and bag2 fibers. Myosin ATPase (and immunofluorescence) staining showed the percentage of permuted chain fibers increased from 0 to 6.7% (5.6%) after 6 wk of training and to 19.2% (14.1%) after 12 wk of training and that it was still at 6.1% (4.2%) 10 wks after training. A novel myosin isoform may thus be expressed in nuclear chain fibers by repetitive recruitment of muscle spindles.     

Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones.

During and after strenuous prolonged exercise, sedentary individuals develop high blood levels of acetoacetate and beta-hydroxybutyrate whereas exercise-trained animals and human subjects do not. We have investigated the possibility that exercise training can increase the capacity of skeletal muscle to oxidize ketones. In this study we measured rates of D-beta[3-14-C]-hydroxybutyrate and [3-14-C]acetoacetate oxidation, and the levels of activity of the enzymes involved in the oxidation of ketones in homogenates of gastrocnemius muscles of exercise-trained and of untrained male rats. The trained animals had markedly lower blood ketone levels immediately and 60 min after a 90 min long bout of exercise than did the sedentary animals. The rates of D-beta-[13-14C]hydroxybutryate and [3-14-C]acetoacetate oxidation were twice as high in homogenates of muscles from the trained as compared to the sedentary rats. The increases in levels of activity in gastrocnemius muscle in response to the exercise program were: beta-hydroxybutyrate dehydrogenase threefold; 3-ketoacid CoA-transferase twofold; and acetoacetyl-CoA thiolase 55%. This exercise-induced increase in the capacity of skeletal muscle to oxidize ketones could play a role in preventing development of ketosis in the physically trained animal during and following prolonged strenuous exercise.     

Efficacy and safety of concurrent training in systemic sclerosis

The optimal training model for patients with systemic sclerosis (SSc) is unknown. In this study, we aimed to investigate the effects of a 12-week combined resistance and aerobic training program (concurrent training) in SSc patients. Eleven patients with no evidence of pulmonary involvement were recruited for the exercise program. Lower and upper limb dynamic strengths (assessed by 1 repetition maximum [1RM] of a leg press and bench press, respectively), isometric strength (assessed by back pull and handgrip tests), balance and mobility (assessed by the timed up-and-go test), muscle function (assessed by the timed-stands test), Rodnan score, digital ulcers, Rayland's phenomenon, and blood markers of muscle inflammation (creatine kinase and aldolase) were assessed at baseline and after the 12-week program. Exercise training significantly enhanced the 1RM leg press (41%) and 1RM bench press (13%) values and back pull (24%) and handgrip strength (11%). Muscle function was also improved (15%), but balance and mobility were not significantly changed. The time-to-exhaustion was increased (46.5%, p = 0.0004), the heart rate at rest condition was significantly reduced, and the workload and time of exercise at ventilatory thresholds and peak of exercise were increased. However, maximal and submaximal &OV0312;o2 were unaltered (p > 0.05). The Rodnan score was unchanged, and muscle enzymes remained within normal levels. No change was observed in digital ulcers and Raynaud's phenomenon. This is the first study to demonstrate that a 12-week concurrent training program is safe and substantially improves muscle strength, function, and aerobic capacity in SSc patients.     

Expression of slow myosin heavy chain during muscle regeneration is not always dependent on muscle innervation and calcineurin phosphatase activity

In the literature, there is an ambiguity as to the respective roles played by calcineurin phosphatase activity (CPA) and muscle innervation in the reestablishment of the slow-twitch muscle phenotype after muscle regeneration in different species. In this study, we wanted to determine the role of calcineurin and muscle innervation on the appearance and maintenance of the slow phenotype during mouse muscle regeneration. The pattern of myosin expression and CPA was analyzed in adult (n=15), regenerating (n=45) and denervated-regenerating (n=32) slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Moreover, in a second group of denervated-regenerating mice (n=9), the animals were treated with a calcineurin inhibitor. Regeneration was induced by injection of cardiotoxin and in the denervated-regenerating group, denervation was carried out by cutting the sciatic nerve before the administration of cardiotoxin. In innervated-regenerating soleus muscle, CPA increased continuously after 10 days postinjury and by 21 days, there was a 3.5-fold increase in CPA compared with adult basal level, whereas in innervated-regenerating EDL muscle, CPA remained unchanged. Moreover, our results show that in denervated-regenerating muscles, the MyHC profile was identical in spite of the functional differences inherent in these muscles. In long-term denervated-regenerating muscles, a slow muscle phenotype was reexpressed both in the presence or absence of calcineurin inhibitor. Our results show that although in innervated-regenerating mouse muscle, the appearance of a slow phenotype is correlated with a peak of CPA, in denervated-regenerating muscles, a slow phenotype is triggered and maintained in a calcineurin- and nerve-independent manner.     

The influence of exercise on muscle lysosomal enzymes

Representative lysosomal enzyme activities were measured in muscles taken 0 h and 24 h after an acute exercise run that was completed without any overt signs of fatigue. The animals had progressed 2 and 4 weeks into a standard exercise program which typically produces adaptive changes in the working muscles. There was an increase in acetylglucosaminidase activity (12%) in the fast-twitch red muscle section of all animals that participated in the training program. This small increase may be representative of a delayed response found after more exhausting exercise. The single exercise bout, however, did not cause any acute change in lysosomal activity nor alter the partition of lysosomal enzymes between the "free" and particulate fractions. Thus, altered lysosomal enzyme activity does not appear to be a contributing influence that challenges muscle fiber homeostasis during moderately intense running.     

Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet.

It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of vitamin C and E supplementation on IL-6 in response to training

Vitamin C and E supplementation has been shown to attenuate the acute exercise-induced increase in plasma interleukin-6 (IL-6) concentration. Here, we studied the effect of antioxidant vitamins on the regulation of IL-6 expression in muscle and the circulation in response to acute exercise before and after high-intensity endurance exercise training. Twenty-one young healthy men were allocated into either a vitamin (VT; vitamin C and E, n = 11) or a placebo (PL, n = 10) group. A 1-h acute bicycling exercise trial at 65% of maximal power output was performed before and after 12 wk of progressive endurance exercise training. In response to training, the acute exercise-induced IL-6 response was attenuated in PL (P < 0.02), but not in VT (P = 0.82). However, no clear difference between groups was observed (group × training: P = 0.13). Endurance exercise training also attenuated the acute exercise-induced increase in muscle-IL-6 mRNA in both groups. Oxidative stress, assessed by plasma protein carbonyls concentration, was overall higher in the VT compared with the PL group (group effect: P < 0.005). This was accompanied by a general increase in skeletal muscle mRNA expression of antioxidative enzymes, including catalase, copper-zinc superoxide dismutase, and glutathione peroxidase 1 mRNA expression in the VT group. However, skeletal muscle protein content of catalase, copper-zinc superoxide dismutase, or glutathione peroxidase 1 was not affected by training or supplementation. In conclusion, our results indicate that, although vitamin C and E supplementation may attenuate exercise-induced increases in plasma IL-6 there is no clear additive effect when combined with endurance training.     

Effects of endurance exercise-training on single-fiber contractile properties of insulin-treated streptozotocin-induced diabetic rats.

The purpose of this study was to characterize the contractile properties of individual skinned muscle fibers from insulin-treated streptozotocin-induced diabetic rats after an endurance exercise training program. We hypothesized that single-fiber contractile function would decrease in the diabetic sedentary rats and that endurance exercise would preserve the function. In the study, 28 rats were assigned to either a nondiabetic sedentary, a nondiabetic exercise, a diabetic sedentary, or a diabetic exercise group. Rats in the diabetic groups received subcutaneous intermediate-lasting insulin daily. The exercise-trained rats ran on a treadmill at a moderate intensity for 60 min, five times per week. After 12 wk, the extensor digitorum longus and soleus muscles were dissected. Single-fiber diameter, Ca(2+)-activated peak force, specific tension, activation threshold, and pCa(50) as well as the myosin heavy chain isoform expression (MHC) were determined. We found that in MHC type II fibers from extensor digitorum longus muscle, diameters were significantly smaller from diabetic sedentary rats compared with nondiabetic sedentary rats (P < 0.001). Among the nondiabetic rats, fiber diameters were smaller with exercise (P = 0.038). The absolute force-generating capacity of single fibers was lower in muscles from diabetic rats. There was greater specific tension (force normalized to cross-sectional area) by fibers from the rats that followed an endurance exercise program compared with sedentary. From the results, we conclude that alterations in the properties of contractile proteins are not implicated in the decrease in strength associated with diabetes and that endurance-exercise training does not prevent or increase muscle weakness in diabetic rats.     

Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle

The purpose of this study was to elucidate the mechanisms underlying low-intensity exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression in rat skeletal muscles. Rats (5-6 wk old) swam without a load and ran on the treadmill at a speed of 13 m/min, respectively, in two 3-h sessions separated by 45 min of rest. PGC-1alpha content in epitrochlearis muscle (EPI) was increased by 75 and 95%, immediately and 6 h after swimming, respectively, with no increase in PGC-1alpha content in the soleus (SOL). After running, PGC-1alpha content in EPI was unchanged, whereas a 107% increase in PGC-1alpha content was observed in SOL 6 h after running. Furthermore, in EPI and SOL as well as other muscles (triceps, plantaris, red and white gastrocnemius), PGC-1alpha expression was enhanced concomitant with reduced glycogen postexercise, suggesting that expression of PGC-1alpha occurs in skeletal muscle recruited during exercise. PGC-1alpha content in EPI was increased after 18-h in vitro incubation with 0.5 mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and 4 mM caffeine. However, AICAR incubation did not affect PGC-1alpha content in the SOL, whereas caffeine incubation increased it. These results suggest that exercise-induced PGC-1alpha expression in skeletal muscle may be mediated by at least two exercise-induced signaling factors: AMPK activation and Ca2+ elevation. The number of factors involved (both AMPK and Ca2+, or Ca2+ only) in exercise-induced PGC-1alpha expression may differ among muscles.     

Angiogenic growth factor expression in rat skeletal muscle in response to exercise training

Angiogenesis occurs in skeletal muscle in response to exercise training. To gain insight into the regulation of this process, we evaluated the mRNA expression of factors implicated in angiogenesis over the course of a training program. We studied sedentary control (n = 17) rats and both sedentary (n = 18) and exercise-trained (n = 48) rats with bilateral femoral artery ligation. Training consisted of treadmill exercise (4 times/day, 1-24 days). Basal mRNA expression in sedentary control muscle was inversely related to muscle vascularity. Angiogenesis was histologically evident in trained white gastrocnemius muscle by day 12. Training produced initial three- to sixfold increases in VEGF, VEGF receptors (KDR and Flt), the angiopoietin receptor (Tie-2), and endothelial nitric oxide synthase mRNA, which dissipated before the increase in capillarity, and a substantial (30- to 50-fold) but transient upregulation of monocyte chemoattractant protein 1 mRNA. These results emphasize the importance of early events in regulating angiogenesis. However, we observed a sustained elevation of the angiopoietin 2-to-angiopoietin 1 ratio, suggesting continued vascular destabilization. The response to exercise was (in general) tempered in high-oxidative muscles. These findings place importance on cellular events coupled to the onset of angiogenesis.     

运动性和高血压性心肌肥大重塑时心肌初级和次级应答基因表达的差异

我们前期研究表明运动性和高血压性心肌肥大细胞表型变化在结构、功能和代谢方面均表现不同,但两者基因表达的不同特征尚不清楚。本实验采用Ｎｏｒｔｈｅｒｎ分子杂交方法对游泳运动１２周大鼠和自发性高血压大鼠（ＳＨＲ）肥大心脏心肌初级和次级应答基因表达进行比较研究。结果表明,游泳大鼠心系数比对照大鼠提高２６％（Ｐ〈０．０１）,心肌ｃ－ｆｏｓ和心房钠尿肽（ＡＮＦ）基因表达在最后一次运动后即刻明显增强,在运动后２