共查询到20条相似文献,搜索用时 31 毫秒
1.
Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers.
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In innervated skeletal muscle fibers, dystrophin and beta-dystroglycan form rib-like structures (costameres) that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural (muscle) agrin whose function is not well understood. In this work, a single application of > or = 10 nM purified recombinant muscle agrin into denervated muscles preserved the transverse orientation of costameric proteins that is typical for innervated muscles, as did a single application of > or = 1 microM neural agrin. At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin. 相似文献
2.
Expression of ACh-activated channels and sodium channels by messenger RNAs from innervated and denervated muscle 总被引:3,自引:0,他引:3
I Parker K Sumikawa C B Gundersen R Miledi 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1988,233(1272):235-246
Xenopus oocytes were used to express polyadenylated messenger RNAs (mRNAs) encoding acetylcholine receptors and voltage-activated sodium channels from innervated and denervated skeletal muscles of cat and rat. Oocytes injected with mRNA from denervated muscle acquired high sensitivity to acetylcholine, whereas those injected with mRNA from innervated muscle showed virtually no response. Hence the amount of translationally active mRNA encoding acetylcholine receptors appears to be very low in normally innervated muscle, but increases greatly after denervation. Conversely, voltage-activated sodium currents induced by mRNA from innervated muscle were about three times larger than those from denervated muscle; this result suggests that innervated muscle contains more mRNA coding for sodium channels. The sodium current induced by mRNA from denervated muscle was relatively more resistant to block by tetrodotoxin. Thus a proportion of the sodium channels in denervated muscle may be encoded by mRNAs different from those encoding the normal channels. 相似文献
3.
4.
A Cangiano L Lutzemberger 《Bollettino della Società italiana di biologia sperimentale》1979,55(19):1946-1949
The origin of the membrane changes induced in skeletal muscle by denervation has been investigated by examining partially denervated rat hindlimb muscles rendered inactive for 2-3 days by a chronic conduction block in the sciatic nerve. Extra-junctional sensitivity to acetylcholine and spike resistance to tetrodotoxin developed to the same extent in the denervated and the adjacent innervated but inactive fibres. On the other hand, impulse-blocked fibres of control muscles not containing denervated fibres showed, at this early time, little membrane changes. These results are interpreted as indicating that the response of muscle to denervation is due to the combined action of inactivity and products of nerve degeneration. 相似文献
5.
Dr. John K. McGeachie 《Cell and tissue research》1989,257(2):455-457
Summary Cellular proliferation in skeletal muscle was measured throughout the first 4 weeks after denervation. Twenty four mice had one leg denervated, and 4 groups of 6 of these mice were injected with tritiated thymidine once daily for 7 days, either during the first, second, third or fourth week after denervation. Autoradiographic labelling of muscle and connective tissue nuclei in denervated muscles was compared with innervated muscles from the opposite innervated legs of the same mice. Labelling of connective tissue and muscle (myonuclear and satellite cell) nuclei was significantly higher in denervated muscles, compared with innervated muscles on the unoperated side. There were no significant differences among labelling of nuclei in muscles denervated for 1, 2, 3 or 4 weeks. However, connective tissue labelling after 1 week of denervation was significantly higher than at later times. This study shows that nuclei of muscle and connective tissue cells proliferate and turnover at high levels for at least one month after denervation. 相似文献
6.
睫状神经营养因子对体外培养骨骼肌细胞的促增殖效应 总被引:2,自引:1,他引:1
邓小华 《中国应用生理学杂志》2000,16(1):59-63
目的 :探讨睫状神经营养因子 (CNTF)对骨骼肌细胞的直接营养作用 ,从而为神经肌肉系统损伤和退行性病变的治疗提供新的思路。结果 :CNTF可以促进体外培养的L6 TG肌母细胞和新生SD大鼠原代骨骼肌细胞增殖。结论 :CNTF对体外骨骼肌细胞具有营养作用。CNTF的神经和肌肉双重营养性能使其可能在神经肌肉损伤和退行性病变的治疗上发挥重要作用。 相似文献
7.
Matar W Lunde JA Jasmin BJ Renaud JM 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,281(1):R56-R65
The objective was to determine whether denervation reduces or enhances the physiological effects of the K(ATP) channel during fatigue in mouse extensor digitorum longus (EDL) and soleus muscle. For this, we measured the effects of 100 microM of pinacidil, a channel opener, and of 10 microM of glibenclamide, a channel blocker, in denervated muscles and compared the data to those observed in innervated muscles from the study of Matar et al. (Matar W, Nosek TM, Wong D, and Renaud JM. Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during fatigue in skeletal muscle. Am J Physiol Cell Physiol 278: C404-C416, 2000). Pinacidil increased the (86)Rb(+) fractional loss during fatigue, and this effect was 2.6- to 3.4-fold greater in denervated than innervated muscle. Pinacidil also increased the rate of fatigue; for EDL the effect was 2.5-fold greater in denervated than innervated muscle, whereas for soleus the difference was 8.6-fold. A major effect of glibenclamide was an increase in resting tension during fatigue, which was for the EDL and soleus muscle 2.7- and 1.9-fold greater, respectively, in denervated than innervated muscle. A second major effect of glibenclamide was a reduced capacity to recover force after fatigue, an effect observed only in denervated muscle. We therefore suggest that the physiological effects of the K(ATP) channel are enhanced after denervation. 相似文献
8.
Neurite outgrowth on cryostat sections of innervated and denervated skeletal muscle 总被引:5,自引:4,他引:1
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
《The Journal of cell biology》1987,105(6):2479-2488
To localize factors that guide axons reinnervating skeletal muscle, we cultured ciliary ganglion neurons on cryostat sections of innervated and denervated adult muscle. Neurons extended neurites on sections of muscle (and several other tissues), generally in close apposition to sectioned cell surfaces. Average neurite length was greater on sections of denervated than on sections of innervated muscle, supporting the existence of functionally important differences between innervated and denervated muscle fiber surfaces. Furthermore, outgrowth was greater on sections of denervated muscle cut from endplate-rich regions than on sections from endplate-free regions, suggesting that a neurite outgrowth-promoting factor is concentrated near synapses. Finally, 80% of the neurites that contacted original synaptic sites (which are known to be preferentially reinnervated by regenerating axons in vivo) terminated precisely at those contacts, thereby demonstrating a specific response to components concentrated at endplates. Together, these results support the hypothesis that denervated muscles use cell surface (membrane and matrix) molecules to inform regenerating axons of their state of innervation and proximity to synaptic sites. 相似文献
9.
Differential Expression of Ciliary Neurotrophic Factor Receptor in Skeletal Muscle of Chick and Rat After Nerve Injury 总被引:1,自引:0,他引:1
Fanny C. F. Ip Amy K. Y. Fu Karl W. K. Tsim Nancy Y. Ip 《Journal of neurochemistry》1996,67(4):1607-1612
Abstract: The activities of ciliary neurotrophic factor (CNTF) were initially thought to be restricted to cells in the nervous system. However, the recent identification of its receptor specificity-conferring α component (CNTFRα) in skeletal muscle has provided the clue to the unexpected actions of CNTF in the periphery. In the present study, we demonstrated that the mRNA expression of CNTFRα in chick skeletal muscle was decreased by ∼10-fold after nerve transection; this finding is in sharp contrast to the dramatic up-regulation observed in denervated rat muscle. As a first step toward investigating the differential regulation of CNTFRα in chick and rat, we examined the mRNA expression of CNTFRα in different types of muscle following nerve injury in young and adult animals. Our findings demonstrated that the differential expression of CNTFRα observed in denervated skeletal muscle of the chick and rat was not dependent on age or muscle type. The temporal profile of the changes in CNTFRα expression was, however, dependent on the age of the chick as well as the types of muscle. Furthermore, the low level of CNTFRα expression observed in denervated chick muscle recovered to almost control levels in regenerating skeletal muscle. Taken together, our findings provided the first extensive analysis on the mRNA expression of CNTFRα and the α subunit of the acetylcholine receptor in various skeletal muscles of the chick following nerve injury and regeneration. 相似文献
10.
Galectin-1 is a soluble carbohydrate-binding protein with a particularly high expression in skeletal muscle. Galectin-1 has
been implicated in skeletal muscle development and in adult muscle regeneration, but also in the degeneration of neuronal
processes and/or in peripheral nerve regeneration. Exogenously supplied oxidized galectin-1, which lacks carbohydrate-binding
properties, has been shown to promote neurite outgrowth after sciatic nerve sectioning. In this study, we compared the expression
of galectin-1 mRNA and immunoreactivity in innervated and denervated mouse and rat hind-limb and hemidiaphragm muscles. The
results show that galectin-1 mRNA expression and immunoreactivity are up-regulated following denervation. The galectin-1 mRNA
is expressed in the extrasynaptic and perisynaptic regions of the muscle, and its immunoreactivity can be detected in both
regions by Western blot analysis. The results are compatible with a role for galectin-1 in facilitating reinnervation of denervated
skeletal muscle. 相似文献
11.
J. P. Leader J. J. Bray A. D. C. Macknight D. R. Mason D. McCaig R. G. Mills 《The Journal of membrane biology》1984,81(1):19-27
Summary Tissue composition, membrane potentials and cellular activity of potassium, sodium and chloride have been measured in innervated and denervated rat skeletal muscles incubatedin vitro. After denervation for 3 days, tissue water, sodium and chloride were increased but cellular potassium content and measured activity were little affected, despite a decrease of 16 mV in resting membrane potential which would have necessitated a decrease in cellular potassium activity of almost 50% were potassium distributed at electrochemical equilibrium. These findings, therefore, preclude a decreased electrochemical potential gradient for potassium as the cause of the membrane depolarization characteristic of denervated muscle fibers. Analysis of the data excludes an important contribution of rheogenic sodium transport to the resting potential of innervated muscles. These results strongly support the hypothesis that the decreased membrane potential in denervated fibers reflects a relative increase in the membrane permeability to sodium. 相似文献
12.
13.
Semaphorins are secreted or transmembrane proteins important for axonal guidance and for the structuring of neuronal systems.
Semaphorin 6C, a transmembrane Semaphorin, has growth cone collapsing activity and is expressed in adult skeletal muscle.
In the present study the expression of Semaphorin 6C mRNA and immunoreactivity has been compared in innervated and denervated
mouse hind-limb and hemidiaphragm muscles. Microscopic localization of immunoreactivity was studied in innervated and denervated
rat skeletal muscle. The results show that Semaphorin 6C mRNA expression and immunoreactivity on Western blots are down-regulated
following denervation. The mRNA of Semaphorin 6C as well as immunoreactivity determined by Western blots are expressed in
extrasynaptic as well as perisynaptic regions of muscle. Immunohistochemical studies, however, show Semaphorin 6C-like immunoreactivity
to be concentrated at neuromuscular junctions. The results suggest a role for Semaphorin 6C in neuromuscular communication. 相似文献
14.
Background
p38 mitogen-activated protein kinase has been implicated in both skeletal muscle atrophy and hypertrophy. T317 phosphorylation of the p38 substrate mitogen-activated protein kinase-activated protein kinase 2 (MK2) correlates with muscle weight in atrophic and hypertrophic denervated muscle and may influence the nuclear and cytoplasmic distribution of p38 and/or MK2. The present study investigates expression and phosphorylation of p38, MK2 and related proteins in cytosolic and nuclear fractions from atrophic and hypertrophic 6-days denervated skeletal muscles compared to innervated controls.Methods
Expression and phosphorylation of p38, MK2, Hsp25 (heat shock protein25rodent/27human, Hsp25/27) and Hsp70 protein expression were studied semi-quantitatively using Western blots with separated nuclear and cytosolic fractions from innervated and denervated hypertrophic hemidiaphragm and atrophic anterior tibial muscles. Unfractionated innervated and denervated atrophic pooled gastrocnemius and soleus muscles were also studied.Results
No support was obtained for a differential nuclear/cytosolic localization of p38 or MK2 in denervated hypertrophic and atrophic muscle. The differential effect of denervation on T317 phosphorylation of MK2 in denervated hypertrophic and atrophic muscle was not reflected in p38 phosphorylation nor in the phosphorylation of the MK2 substrate Hsp25. Hsp25 phosphorylation increased 3-30-fold in all denervated muscles studied. The expression of Hsp70 increased 3-5-fold only in denervated hypertrophic muscles.Conclusions
The study confirms a differential response of MK2 T317 phosphorylation in denervated hypertrophic and atrophic muscles and suggests that Hsp70 may be important for this. Increased Hsp25 phosphorylation in all denervated muscles studied indicates a role for factors other than MK2 in the regulation of this phosphorylation.15.
Cynthia L. Jordan 《Developmental neurobiology》1996,31(1):29-40
In adult skeletal muscles, exogenous ciliary neurotrophic factor (CNTF) induces axons and their nerve terminals to sprout. CNTF also regulates the amount of multiple innervation in developing skeletal muscles during synapse elimination, maintaining multiple innervation of muscle fibers. While CNTF may maintain multiple innervation by regulating developmental synapse elimination, it is also possible that CNTF induces the formation of new multiple innervation through a sprouting response. In this study I examined morphologically the effects of CNTF during synapse elimination in the extensor digitorum longus (EDL) muscle. Rat pups received injections of CNTF in one leg and vehicle in the other either early [postnatal day 7 (P7)-P13] or late (P14–P20) in development. The early treatment period corresponds to that time when the pattern of innervation in the EDL is converted from predominantly multiple to single innervation. The late treatment period is at the end of synapse elimination for the EDL but corresponds to the major period of synapse elimination in the levator ani (LA), allowing a comparison of effects on these two muscles from the same animals. On the day after the final injection, EDL muscles were dissected and stained with tetranitroblue tetrazolium and the resulting pattern of innervation was assessed. The present findings indicate that only the early CNTF treatment regulates the level of multiple innervation in the EDL. Moreover, the effect of early CNTF treatment was local, affecting multiple innervation only in the EDL from the CNTF-treated leg. CNTF injected during the late treatment period had no apparent effects on the EDL but had a potent effect on the pattern of innervation in the LA, significantly increasing the level of multiple innervation in this muscle. Thus, CNTF affected multiple innervation in these two muscles only if provided during the period when single innervation normally develops. There was no evidence to indicate that CNTF induced axons or their terminals to sprout during either treatment period. In conclusion, CNTF increases the level of multiple innervation, probably by regulating synapse elimination, and skeletal muscles themselves may be an important target site for CNTF action. Presumably, the sprouting response to CNTF found in adult muscle develops sometime after P21. © 1996 John Wiley & Sons, Inc. 相似文献
16.
Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses 总被引:21,自引:6,他引:21
To elucidate the nature of signals that control the level and spatial distribution of mRNAs encoding acetylcholine receptor (AChR), alpha-, beta-, gamma-, delta- and epsilon-subunits in muscle fibers chronic paralysis was induced in rat leg muscles either by surgical denervation or by different neurotoxins that cause disuse of the muscle or selectively block neuromuscular transmission pre- or postsynaptically and cause an increase of AChRs in muscle membrane. After paralysis, the levels and the spatial distributions of the different subunit-specific mRNAs change discoordinately and seem to follow one of three different patterns depending on the subunit mRNA examined. The level of epsilon-subunit mRNA and its accumulation at the end-plate are largely independent on the presence of the nerve or electrical muscle activity. In contrast, the gamma-subunit mRNA level is tightly coupled to innervation. It is undetectable or low in innervated normally active muscle and in innervated but disused muscle, whereas it is abundant along the whole fiber length in denervated muscle or in muscle in which the neuromuscular contact is intact but the release of transmitter is blocked. The alpha-, beta-, and delta-subunit mRNA levels show a different pattern. Highest amounts are always found at end-plate nuclei irrespective of whether the muscle is innervated, denervated, active, or inactive, whereas in extrasynaptic regions they are tightly controlled by innervation partially through electrical muscle activity. The changes in the levels and distribution of gamma- and epsilon-subunit-specific mRNAs in toxin-paralyzed muscle correlate well with the spatial appearance of functional fetal and adult AChR channel subtypes along the muscle fiber. The results suggest that the focal accumulation at the synaptic region of mRNAs encoding the alpha-, beta-, delta-, and epsilon-subunits, which constitute the adult type end-plate channel, is largely determined by at least two different neural factors that act on AChR subunit gene expression of subsynaptic nuclei. 相似文献
17.
The effect of tetrodotoxin (TTX) (10(-5)-10(-6)M) on the mechanical activity and on the action potential of innervated and denervated muscle of the rat was studied. The twitch tension was reduced to 10 % of the control values within 20 min of TTX 10(-6) introduction. This effect was reversible. The mean twitch tension in the presence of 10(-6)M TTX expressed as a percentage of control was 9.3 +/- 2.4 (SEM) for innervated muscle and 10.9 +/- 2.5 for denervated muscle. The dose-effect twitch relation for denervated muscles was not significantly different from that observed in control innervated muscles in the 10(-3)-10(-6) TTX range. Action potentials of innervated muscles could not be elicited in 10(-6)M TTX. In the presence of this (TTX) fibers of chronically denervated muscles consistently responded to stimulation with action potentials which were slower and smaller but still with overshoot, contrasting with fibrillation potentials that had been described to be blocked by TTX. 相似文献
18.
Fenyvesi R Rácz G Wuytack F Zádor E 《Biochemical and biophysical research communications》2004,320(2):599-605
The level of active subunit of calcineurin and the calcineurin (Cn) enzyme activity are increased in innervated but not in denervated slow type regenerating skeletal soleus muscle. These nerve-dependent increases were not accompanied by similar increases in the mRNA levels. The changes in the mRNA level of the modulatory calcineurin interacting protein, MCIP1.4, reflected the calcineurin activity and did not increase in denervated regenerating muscles compared to the innervated regenerating controls. The increases in Cn activity and in MCIP1.4 mRNA levels occurred before the switch from fast to slow-type myosin heavy chain isoforms, a phenomenon similarly known to be dependent on innervation. This highlights the role of mediators, acting between the nerve and calcineurin, in the formation of slow fiber identity. 相似文献
19.
Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor in vitro 总被引:11,自引:0,他引:11
Chen X Mao Z Liu S Liu H Wang X Wu H Wu Y Zhao T Fan W Li Y Yew DT Kindler PM Li L He Q Qian L Wang X Fan M 《Molecular biology of the cell》2005,16(7):3140-3151
Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells--they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These "progenitor cells" retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway. 相似文献
20.
Four weeks after denervation, various changes were observed in the phospholipid composition of the sarcolemmal and sarcoplasmic fractions of skeletal muscles with different functions. Neurotomy also affected the innervated contralateral muscles and produced opposite changes in the phospholipid content of subcellular fractions. The increase in the amount of phospholipids in the sarcolemmal fractions of the denervated muscles was only apparent. The difference between the denervated and contralateral muscles was also due to the decrease of phospholipids in the contralateral muscles. These changes were more pronounced in the tetanic (fast-twitch) than in the tonic (slow-twitch) muscles. In the sarcoplasmic fraction of the denervated tetanic muscle an increase, while in that of the tonic one a slight decrease of phospholipids appeared. In contrast, the phospholipid content in the sarcoplasmic fractions of contralateral muscles did not decrease, while it increased slightly in the tonic muscle. The amount of plasmalogens (fatty aldehyde: lipid phosphorus ratio) decreased only in the subcellular fractions of the denervated muscles while there was no change in those of the contralateral muscles. 相似文献