HSF expression in skeletal muscle during myogenesis: Implications for failed regeneration in old mice

HSF expression in skeletal muscle during myogenesis: Implications for failed regeneration in old mice
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DOI:
10.1016/j.exger.2006.02.002
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发表时间:
2006-05-01
影响因子:
3.9
通讯作者:
Jackson, Malcolm J.
Jackson, Malcolm J.
中科院分区:
医学2区
文献类型:
--
作者:
McArdle, Anne;Broome, Caroline S.;Jackson, Malcolm J.

文献摘要

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老年小鼠肌肉在严重损伤后恢复力量产生的能力严重受损,特别是在再生的后期。这种无法成功恢复的原因可能与老年小鼠肌肉产生热休克蛋白(HSPs)的能力减弱有关,因为过度表达HSP70的老年小鼠肌肉在损伤后成功恢复。成熟哺乳动物骨骼肌损伤后再生的能力是由于成熟骨骼肌纤维外围存在未分化的单核成肌前体细胞(卫星细胞)所致。HSP的表达受热休克因子1和2(HSF1和HSF2)的初级转录控制。本研究的目的是通过Western blotting检测热休克因子1和2在小鼠来源的C2C12成肌细胞中的表达,作为研究骨骼肌再生的实验模型系统。数据表明,在再生的早期阶段,肌管中HSF2的含量显著增加。相反,在再生过程中,肌管中的HSF1含量一直保持在相对较低的水平。因此,HSF1的异常激活可能在老年小鼠肌肉再生缺陷中发挥作用。(C)2006 Elsevier Inc.保留所有权利。
The ability of muscles of old mice to recover force generation following substantial damage is severely impaired, particularly during the late phase of regeneration. This inability to recover successfully may be associated with the attenuated ability of muscles of old mice to produce heat shock proteins (HSPs) in response to stress since muscles of old mice overexpressing HSP70 recover successfully following damage. The capacity of mature mammalian skeletal muscle to regenerate following damage is due to the presence of undifferentiated mononuclear myogenic precursor cells (satellite cells) at the periphery of mature skeletal muscle fibres. HSP expression is under the primary transcriptional control of heat shock factors 1 and 2 (HSF1 and HSF2). The aim of this study was to examine the expression of heat shock factors 1 and 2 by western blotting in mouse-derived C2C12 myoblasts as an experimental model system for investigating skeletal muscle regeneration. Data demonstrated that the HSF2 content of myotubes was significantly increased during the early stages of regeneration. In contrast, the HSF1 content of myotubes remained relatively low until late during regeneration. Thus, abnormal activation of HSF1 may play a role in the defective regeneration seen in muscles of old mice. (c) 2006 Elsevier Inc. All rights reserved.