Dystroglycan glycosylation and its role in matrix binding in skeletal muscle

Dystroglycan is an essential component of the dystrophin-glycoprotein complex. Three glycan sequencing studies have identified O-linked mannose chains, including NeuAcalpha 2,3Galbeta 1,4GlcNAcbeta 1,2Manalpha-O, on alpha dystroglycan. Chemical deglycosylation of alpha dystroglycan, antibody blocking studies, and glycan blocking studies all suggest that the O-linked glycans on alpha dystroglycan mediate the binding of extracellular matrix proteins in skeletal muscle. Structural data on laminin G domains and agrin-binding studies also suggest this is the case. Dystroglycan, however, is able to bind proteins via mechanisms that do not involve O-linked glycans. Moreover, laminin and other matrix proteins can bind cell adhesion molecules via their glycan chains. Thus although complex and sometimes not overly convincing, these data suggest that glycosylation plays an important role in dystroglycan binding and function in skeletal muscle.     

The formation of intracristal structures induced in skeletal muscle mitochondria by high pressure

Following the application of high pressure to skeletal muscle for extended periods, intracristal structures are found in the mitochondria. In addition, electron dense granules of 70–170 nm diameter are found in the matrix of these mitochondria. In contrast, pressure-treated liver mitochondria show only large (300–400 nm) matrix granules but not the intracristal structures. Both the inner and outer mitochondrial membranes appear intact after pressure-treatment. Short periods of pressuretreatment have little effect on either the morphology of mitochondria or the pH of the tissues. It is suggested that the formation of the intracristal structures may be due to the effects of pH rather than pressure alone. This finding raises the possibility that intracristal structures may occur as a preparative artefact particularly where the tissue has undergone considerable manipulation.     

Rapid biphasic arteriolar dilations induced by skeletal muscle contraction are dependent on stimulation characteristics

To test the hypothesis that measurable changes in microvasculature dilation occur in response to a single short-duration tetanic contraction, we contracted three to five skeletal muscle fibres of the hamster cremaster muscle microvascular preparation (in situ) and evaluated the response of an arteriole overlapping the active muscle fibres. Arteriolar diameter (baseline diameter = 16.4 +/- 0.9 micro m, maximum diameter = 34.7 +/- 1.2 micro m) was measured before and after a single contraction resulting from a range of stimulus frequencies (4, 10, 20, 30, 40, 60, and 80 Hz) within a 250- or 500-ms train. Four and 10 Hz produced a significant dilation at 2.9 +/- 0.4 and 6.5 +/- 2.8 s, respectively, within a 250-ms train and 3.0 +/- 0.2 and 6.1 +/- 1.3 s, respectively, within a 500-ms train. Biphasic dilations were observed within a 250-ms train at 20 Hz (at 3.9 +/- 0.9 and 22.1 +/- 4.3 s), 30 Hz (at 2.7 +/- 0.3 and 17.5 +/- 2.9 s), and 40 Hz (at 3.8 +/- 0.4 and 23.2 +/- 2.6 s) and within a 500-ms train at 20 Hz (at 4.8 +/- 0.4 and 31.9 +/- 3.8 s) and 30 Hz (at 3.4 +/- 0.3 and 27.6 +/- 3.0 s). A single dilation was observed within a 250-ms train at 60 Hz (at 5.1 +/- 0.7 s) and 80 Hz (at 14.2 +/- 3.3 s) and within a 500-ms train at 40 Hz (at 9.9 +/- 3.2 s), 60 Hz (at 7.9 +/- 2.1 s), and 80 Hz (at 13.4 +/- 4.0 s). We have shown that a single contraction ranging from a single twitch (4 Hz, 250 ms) to fused tetanic contractions produces significant arteriolar dilations and that the pattern of dilation is dependent on the stimulus frequency and train duration.     

MicroRNAs in skeletal muscle biology and exercise adaptation

MicroRNAs (miRNAs) have emerged as important players in the regulation of gene expression, being involved in most biological processes examined to date. The proposal that miRNAs are primarily involved in the stress response of the cell makes miRNAs ideally suited to mediate the response of skeletal muscle to changes in contractile activity. Although the field is still in its infancy, the studies presented in this review highlight the promise that miRNAs will have an important role in mediating the response and adaptation of skeletal muscle to various modes of exercise. The roles of miRNAs in satellite cell biology, muscle regeneration, and various myopathies are also discussed.     

Disrupted autophagy undermines skeletal muscle adaptation and integrity

This review assesses the importance of proteostasis in skeletal muscle maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be particularly vulnerable to genetic defects in basal and induced autophagy, indicating that autophagy is co-substantial to skeletal muscle maintenance and adaptation. We discuss emerging evidence that tension-induced protein unfolding may act as a direct link between mechanical stress and autophagic pathways. Mechanistic links between protein damage, autophagy and muscle hypertrophy, which is also induced by mechanical stress, are still poorly understood. However, some mouse models of muscle disease show ameliorated symptoms upon effective targeting of basal autophagy. These findings highlight the importance of autophagy as therapeutic target and suggest that elucidating connections between protein unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely to reveal specific therapeutic windows for the treatment of muscle wasting disorders.     

Hematopoietic potential cells in skeletal muscle

During mouse embryogenesis, the formation of primitive hematopoiesis begins in the yolk sac on embryonic day 7.5 （E7.5）. Thereafter, definitive hematopoietic stem cell （HSC） activity is first detectable in the aorta-gonadmesonephros （AGM） region on E10, followed by fetal liver and yolk sac. Subsequently, the fetal liver by E12 becomes the main tissue for definitive hematopoiesis. At a later time, HSC population in the fetal liver migrates to the bone marrow, which becomes the major site of hematopoiesis throughout normal adult life.[第一段]     

Role of matrix metalloproteinases in skeletal muscle

Matrix metalloproteases (MMPs) are key regulatory molecules in the formation, remodeling, and degradation of extracellular matrix (ECM) components in both physiological and pathological processes in many tissues. In skeletal muscle, MMPs play an important role in the homeostasis and maintenance of myofiber functional integrity by breaking down ECM and regulating skeletal muscle cell migration, differentiation and regeneration. Skeletal muscle satellite cells, a group of quiescent stem cells located between the basement membrane and the plasmalemma of myofibers, are responsible for lifelong maintenance and repairing, which can be activated and as a result migrate underneath the basement membrane to promote regeneration at the injured site. MMPs are able to degrade ECM components, thereby facilitating satellite cell migration and differentiation. This current review will focus on the critical roles of MMPs in skeletal muscle injury and repair, which include satellite cell activation with migration and differentiation. The effect of MMPs on muscle regeneration and fibrous scar tissue formation, as well as therapeutic insights for the future will be explored.     

Chronic muscle stimulation increases lactate transport in rat skeletal muscle

The aim of this study was to examine the effects of chronic low frequency stimulation on the lactate transport across the plasma membrane of the tibialis anterior (TA) muscle of the rat. Stimulating electrodes were implanted on either side of the peroneal nerve in one hindlimb. Chronic stimulation (10 Hz, 50 psec bursts, 24 h/day) commenced 7 days after surgery, and were continued for 7 days. Animals were then left for 24 h, and thereafter muscles were obtained. Cytochrome C-oxidase activity was increased 1.9-fold in the stimulated TA compared to the control TA (p < 0.05). Lactate transport (zero-trans) was measured in giant sarcolemmal vesicles obtained from the chronically stimulated TA and the control TA. At each of the concentrations used in these studies a significant increase in lactate transport was observed: 2.8-fold increase at 1 mM lactate p < 0.05); 2-fold increases at both 30 mM and 50 mM lactate p < 0.05). These studies have shown that lactate transport capacity is markedly increased in response to chronic muscle contraction.     

Mechanical signal transduction in skeletal muscle growth and adaptation.

The adaptability of skeletal muscle to changes in the mechanical environment has been well characterized at the tissue and system levels, but the mechanisms through which mechanical signals are transduced to chemical signals that influence muscle growth and metabolism remain largely unidentified. However, several findings have suggested that mechanical signal transduction in muscle may occur through signaling pathways that are shared with insulin-like growth factor (IGF)-I. The involvement of IGF-I-mediated signaling for mechanical signal transduction in muscle was originally suggested by the observations that muscle releases IGF-I on mechanical stimulation, that IGF-I is a potent agent for promoting muscle growth and affecting phenotype, and that IGF-I can function as an autocrine hormone in muscle. Accumulating evidence shows that at least two signaling pathways downstream of IGF-I binding can influence muscle growth and adaptation. Signaling via the calcineurin/nuclear factor of activated T-cell pathway has been shown to have a powerful influence on promoting the slow/type I phenotype in muscle but can also increase muscle mass. Neural stimulation of muscle can activate this pathway, although whether neural activation of the pathway can occur independent of mechanical activation or independent of IGF-I-mediated signaling remains to be explored. Signaling via the Akt/mammalian target of rapamycin pathway can also increase muscle growth, and recent findings show that activation of this pathway can occur as a response to mechanical stimulation applied directly to muscle cells, independent of signals derived from other cells. In addition, mechanical activation of mammalian target of rapamycin, Akt, and other downstream signals is apparently independent of autocrine factors, which suggests that activation of the mechanical pathway occurs independent of muscle-mediated IGF-I release.     

Endogenous triacylglycerol utilization by rat skeletal muscle during tetanic stimulation

An isolated perfused rat hindquarter preparation was used to examine the utilization of endogenous triacylglycerol (TG) during 20 min of electrical stimulation. The sciatic nerve was stimulated with maximal tetanic trains at 0.5 Hz. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded, and muscle samples were taken pre- and poststimulation. Twenty minutes of stimulation significantly reduced endogenous TG from 6.78 +/- 0.84 to 4.64 +/- 0.64 mumol X g dry wt-1 (32%) in the red gastrocnemius muscle and from 7.70 +/- 0.61 to 6.66 +/- 0.80 mumol X g dry wt-1 (13.5%) in the plantaris muscle. Although TG content decreased by 16% in the soleus (28.2 +/- 5.0 to 23.8 +/- 4.4 mumol X g-1), the change was not significant. Stimulation had no effect on white gastrocnemius TG concentration (6.84 +/- 1.22 to 6.25 +/- 1.41 mumol X g-1). Thus oxidation of TG occurred primarily in muscles with a large proportion of fast-twitch oxidative-glycolytic fibers. Calculations from measurements of muscle energy stores and fuel uptake indicated that up to 62% of the aerobic energy was provided by endogenous TG. Carbohydrate oxidation contributed up to 28% and the remaining 10% may be accounted for by the oxidation of exogenous free fatty acids originating in the perfusate or from hindquarter adipose tissue. The magnitude of the fall in TG concentration in a given muscle was inversely related to the fall in glycogen concentration.