Hyperplasia and hypertrophy in the growth of skeletal muscle in juvenile Atlantic salmon, Salmo salar L.

Both red and white muscle fibre numbers in juvenile Atlantic salmon increased gradually with fish length throughout the freshwater growth period. Mean fibre area increased as fish grew to 6.5 cm f.l. , but thereafter was unrelated to fish length. Hyperplasia was most obvious when fish were growing fastest, and was the dominant growth process in fish over 6.5 cm f.l. Hypertrophy was most important when growth was slow, as in autumn and winter.
Mean white fibre area was significantly smaller in deep muscle than at medial and superficial sites. Total cross-sectional area of red, white and total trunk muscle increased with fish length. The ratio of red: white cross-sectional area increased with fish length to a plateau at about 10% after 6.5 cm f.l.     

Signaling pathways controlling skeletal muscle mass

Abstract

The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy”, is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.     

肌球蛋白抑制剂BDM对骨骼肌收缩功能的非特异性作用

目的:探讨萎缩骨骼肌单位面积上等长收缩最大张力(Pt)降低的机理.方法:采用肌球蛋白ATP酶抑制剂BDM(Butanedione monoxime)灌流,观测其对离体骨骼肌肌条等长收缩功能的影响.结果:研究表明,BDM可使比目鱼肌(SOL)与趾长伸肌(EDL)等长收缩Pt明显降低,BDM对骨骼肌收缩功能的抑制呈剂量依赖性关系,且完全可逆.低浓度BDM(1 mmol/L)仅降低骨骼肌等长收缩的Pt而不影响其收缩时程,高浓度(10 mmol/L)下使收缩时程明显缩短.与SOL相比,在10mmol/LBDM作用下,使EDL等长收缩Pt降低一半的时间明显加快.无论在低浓度还是高浓度下,BDM对EDL肌球蛋白ATP酶活性的抑制作用均大于SOL.在相同浓度下,BDM对Pt的抑制程度远远大于对肌球蛋白ATP酶活性的抑制.结论:这些结果提示骨骼肌横桥功能降低可能是其等长收缩pt下降的原因之一;BDM并非特异型肌球蛋白ATP酶抑制剂,可对兴奋-收缩偶联的多个环节产生影响.     

Cooperative mechanisms in the activation dependence of the rate of force development in rabbit skinned skeletal muscle fibers

Regulation of contraction in skeletal muscle is a highly cooperative process involving Ca(2+) binding to troponin C (TnC) and strong binding of myosin cross-bridges to actin. To further investigate the role(s) of cooperation in activating the kinetics of cross-bridge cycling, we measured the Ca(2+) dependence of the rate constant of force redevelopment (k(tr)) in skinned single fibers in which cross-bridge and Ca(2+) binding were also perturbed. Ca(2+) sensitivity of tension, the steepness of the force-pCa relationship, and Ca(2+) dependence of k(tr) were measured in skinned fibers that were (1) treated with NEM-S1, a strong-binding, non-force-generating derivative of myosin subfragment 1, to promote cooperative strong binding of endogenous cross-bridges to actin; (2) subjected to partial extraction of TnC to disrupt the spread of activation along the thin filament; or (3) both, partial extraction of TnC and treatment with NEM-S1. The steepness of the force-pCa relationship was consistently reduced by treatment with NEM-S1, by partial extraction of TnC, or by a combination of TnC extraction and NEM-S1, indicating a decrease in the apparent cooperativity of activation. Partial extraction of TnC or NEM-S1 treatment accelerated the rate of force redevelopment at each submaximal force, but had no effect on kinetics of force development in maximally activated preparations. At low levels of Ca(2+), 3 microM NEM-S1 increased k(tr) to maximal values, and higher concentrations of NEM-S1 (6 or 10 microM) increased k(tr) to greater than maximal values. NEM-S1 also accelerated k(tr) at intermediate levels of activation, but to values that were submaximal. However, the combination of partial TnC extraction and 6 microM NEM-S1 increased k(tr) to virtually identical supramaximal values at all levels of activation, thus, completely eliminating the activation dependence of k(tr). These results show that k(tr) is not maximal in control fibers, even at saturating [Ca(2+)], and suggest that activation dependence of k(tr) is due to the combined activating effects of Ca(2+) binding to TnC and cross-bridge binding to actin.     

Effects of growth hormone on skeletal muscle

Human growth hormone (GH) is widely abused as a performance-enhancing anabolic drug by athletes and bodybuilders. However, the effects of GH on skeletal muscle mass, strength and fibre composition remain unclear. We therefore summarize in the following the current knowledge on the physiological role of GH in the regulation of skeletal muscle growth and function and evaluate its potential therapeutic potency as a muscle anabolic hormone. In states of GH deficiency, reduced muscle mass and strength are characteristic findings which can be reversed successfully by the supplementation of GH. In contrast, the currently available data suggest that GH administration alone or in combination with strength exercise has little, if any, effect on muscle volume, strength and fibre composition in non-GH-deficient healthy young individuals. This assumption is supported by the lack of evidence for a significant performance-enhancing effect of GH in athletes. However, further studies will be necessary to define patient populations which might benefit from GH treatment like frail elderly individuals in whom a GH-induced change into a more youthful muscle fibre composition has been reported.     

Interaction between zinc and calcium in skeletal muscle in young growing rats

The purpose of the present study was to determine whether zinc and calcium could interact at the tissue level. In the first part of the study, adult rats were injected with ZnCl₂ dissolved in a physiological saline solution to determine the effects of Zn on Ca levels in various tissues. In the second part of the study, weaned rats (at day 22 postnatally) were fed a diet supplemented with Zn until day 50 and were then sacrificed. In both instances, blood, brain, heart, liver, and skeletal muscle were taken and analyzed. In the Zn-injected group, the brain, heart, and liver showed no interaction between Zn and Ca. The skeletal muscle, in contrast, showed a decrease in Ca in the homogenate, whereas Zn contents showed a significant increase at the sarcoplasmic reticulum (SR). Likewise, in the Zn-supplemented group, the Zn content of the SR vesicle of the skeletal muscle showed an increase, whereas Ca content of the pellet (14,000 g), which contains cell debris, nucleus, mitochondria, and SR vesicles of this group, showed a decrease. Current findings suggest antagonistic effects between Zn and Ca on this tissue. Zn may play a critical role in cellular function through the alteration of itnracellular distribution of Ca in skeletal muscle.     

Alterations of proteasome activities in skeletal muscle tissue of diabetic rats

During the last years many investigations have shown that a major catalyst within the mechanism of skeletal muscle wasting occuring under conditions like sepsis, injuries, trauma, cancer cachexia, chronic acidosis, fasting, glucocorticoid treatment, and insulinopenia is the ubiquitin-proteasome system. Evidence for this was obtained by findings that the rate of ATP-dependent protein degradation is increased, that m-RNA concentrations of several proteasome subunits and ubiquitin are increased and the amount of ubiquitin-protein conjugates is elevated under these conditions. Additionally, the enhanced protein breakdown was shown to be suppressed by proteasome inhibitors. In the present report we show that most but not all of the proteolytic activities of partially purified 20S/26S proteasomes from skeletal muscle of rats increase after induction of Diabetes mellitus. This finding suggests that part of the mechanism of acceleration of muscle protein breakdown is due to changes in proteasome activities.     

猪的骨骼肌生长发育研究进展

瘦肉率对生猪产业来说是一个极其重要的经济指标,而这一指标完全取决于骨骼肌的生长发育。因此,猪骨骼肌生长发育机理的研究是十分必要的。然而,在早期由于各种因素的限制,猪骨骼肌单个基因的研究一直进展缓慢;相反,以小鼠为模型,其骨骼肌单基因的功能研究却取得了较大进展。在这一时期,影响肌决定和肌分化的基因,如MRFs家族和MEF2家族相继被发现,这些基因在猪的肌肉发育中也发挥着同样的作用。然而,这些结果并不能很好地揭示骨骼肌发育过程中复杂的基因间互作关系。随着近年来芯片和测序技术的不断发展,更多人试图从整个转录谱的水平来阐述猪肌肉发育的分子机理,并且也取得了较大的进展。为了对猪骨骼肌生长发育有一个更为清晰的认识,该文将以目前猪骨骼肌生长发育研究结果为基础,同时结合模式动物小鼠骨骼肌单基因的研究成果,对猪的骨骼肌生长发育分子调控机理进行详细的阐述。     

Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders

Interleukin-15 (IL-15) is a novel anabolic factor for skeletal muscle which inhibits muscle wasting associated with cancer (cachexia) in a rat model. To develop a cell culture system in which the mechanism of the anabolic action of IL-15 on skeletal muscle could be examined, the mouse C2 skeletal myogenic cell line was transduced with a retroviral expression vector for IL-15 and compared to sister cells transduced with a control vector. Overexpression of IL-15 induced fivefold higher levels of sarcomeric myosin heavy chain and alpha-actin accumulation in differentiated myotubes. Secreted factors from IL-15-overexpressing myogenic cells, but not from control cells, induced increased myofibrillar protein accumulation in cocultured control myotubes. IL-15 overexpression induced a hypertrophic myotube morphology similar to that described for cultured myotubes which overexpressed the well-characterized anabolic factor insulin-like growth factor-I (IGF-I). However, in contrast to IGF-I, the hypertrophic action of IL-15 on skeletal myogenic cells did not involve stimulation of skeletal myoblast proliferation or differentiation. IL-15 induced myotube hypertrophy at both low and high IGF-I concentrations. Furthermore, in contrast to IGF-I, which stimulated only protein synthesis under these culture conditions, IL-15 both stimulated protein synthesis and inhibited protein degradation in cultured skeletal myotubes. These findings indicate that IL-15 action on skeletal myogenic cells is distinct from that of IGF-I. Due to the ability of IGF-I to stimulate cell division and its association with several forms of cancer, controversy exists concerning the advisability of treating cachexia or age-associated muscle wasting with IGF-I. Administration of IL-15 or modulation of the IL-15 signaling pathway may represent an alternative strategy for maintaining skeletal muscle mass under these conditions.     

耐力运动对大鼠骨骼肌ERK1/2活性的影响

目的:探讨耐力运动对大鼠骨骼肌蛋白总量(t-ERK1/2)及磷酸化ERK1/2(p-ERK1/2)及ERK2mRMA表达的影响。方法:SD大鼠随机分为对照组和运动组。运动组分为1h/d和1.5h/d组,共7周,运动结束后24h和48h取材,测定葡萄糖和胰岛素浓度;Westernblot法检测骨骼肌t-ERK1/2、p-ERK1/2蛋白表达;RT-PCR法分析ERK2mRNA表达。结果:与对照组比较,运动组胰岛素浓度降低;各运动组p-ERK1/2升高;1.5h/d-24h和-48h组t-ERK1/2增高;1h/d-24h组与1.5h/d-24h和-48hERK2mRNA表达增高。结论:耐力运动可能通过增加ERK1/2活性,提高大鼠骨骼肌对胰岛素的敏感性。     

A novel cell-based system for evaluating skeletal muscle cell hypertrophy-inducing agents

Skeletal muscle is a tissue that adapts to increased use by increasing contractile protein gene expression and ultimately skeletal muscle mass (hypertrophy). To identify hypertrophy-inducing agents that may be potentially useful in the treatment of age-related muscle loss (sarcopenia) and to better understand hypertrophy signal transduction pathways, we have created a skeletal muscle cell-based hypertrophy-responsive system. This system was created by permanently modifying the relatively undifferentiated C2C12 cell line so that it contains the beta-myosin heavy chain (beta-MHC) gene promoter and enhancer regions fused to a luciferase reporter gene. This cell line responds, by increasing luciferase expression, to a variety of skeletal muscle hypertrophy-inducing agents, including insulin, insulin-like growth factor I, testosterone, and the beta-adrenergic receptor agonist isoproterenol, in both the undifferentiated and differentiated states. This cell-based system should be useful for identifying novel hypertrophy-inducing agents as well as understanding hypertrophy signal transduction.     

Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy

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骨骼肌生长调控信号通路

骨骼肌能够根据环境刺激的变化改变其质量,可以通过细胞融合或提高蛋白质水平来增加它的大小。介绍了参与骨骼肌生长发育调控的两个关键性信号通路——胰岛素样生长因子1和肌肉生长抑制素信号通路中新的且重要的研究结果,这对于了解肌肉的发育和成年期肌肉稳态的维持,并寻找肌肉相关疾病潜在的治疗靶点非常有意义。     

Effects of membrane potential on just detectable movement in rat skeletal muscle: Effects of denervation

The potential, Vt, at which a brief test depolarization first elicited movement was determined using two-microelectrode point voltage clamp. We expected that inactivation of excitation-contraction coupling at conditioning potentials between ?60 and 0 mV would shift Vt to more positive potentials, and that fibers would become inactivatable with less conditioning depolarization in EDL than soleus. The curve relating Vt to conditioning potential had a negative slope (which was insensitive to addition of 1 mm cobalt or replacement of calcium with 20 mm CaEGTA) between ?60 and ?35 mV and a steep positive slope with further depolarization. Unexpectedly, fibers became inactivatable with less conditioning depolarization in soleus than in EDL when Vt was measured with 50 msec test pulses. However, the positive shift in Vt became less steep as test pulse duration lengthened in soleus fibers. When Vt obtained with test pulses approaching rheobase (10 msec in EDL and 500 msec in soleus) was compared, EDL fibers became inactive with less conditioning depolarization than soleus fibers. The increase in Vt became steeper with 1 mm cobalt or 20 mm CaEGTA and was shifted to more positive potentials by denervation in soleus fibers. We conclude that inactivation (i) does not strongly influence threshold contractions at conditioning potentials between ?60 and ?40 mV and (ii) influences Vt between ?40 and 0 mV in a manner that depends on test pulse duration.