The role of calcium and calcium/calmodulin-dependent kinases in skeletal muscle plasticity and mitochondrial biogenesis
The role of calcium and calcium/calmodulin-dependent kinases in skeletal muscle plasticity and mitochondrial biogenesis
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DOI：
10.1079/pns2004335
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发表时间：
2004-05-01
影响因子：
7
通讯作者：
Chin, ER
中科院分区：
文献类型：
--
作者：
Chin, ER
细胞内Ca ~（2+）在骨骼肌兴奋-收缩偶联和兴奋-转录偶联中起重要作用。由于增加负荷（即阻力或耐力训练）或减少活动（即固定或损伤）导致的肌肉基因表达的活动依赖性改变与肌肉兴奋水平密切相关。慢肌纤维和快肌纤维中基因的差异表达也依赖于纤维激活。因此，这两种生物现象都与Ca 2+瞬变的幅度和持续时间紧密相关，这是一种由Ca 2+依赖性转录途径解码的下游信号。越来越多的证据表明，钙调神经磷酸酶-活化T细胞核因子途径和Ca 2 +/钙调蛋白依赖性激酶（CaMK）11和IV在调节氧化酶表达、线粒体生物合成和纤维型特异性肌原纤维蛋白表达中起重要作用。已知CaMKII解码频率依赖性信息，并且在肥大生长和耐力适应期间被激活。因此，据推测，CaMKII，并可能CaMKIV，在肌肉萎缩和表达水平的CaMKII α，-II β，-II γ和-IV进行了评估，在骨骼肌从年轻，老年和去神经大鼠下调。结果表明，CaMKII gamma在衰老和去神经比目鱼肌中上调，而CaMKII alpha或-β则没有上调，并且CaMKIV在骨骼肌中不存在，但在心肌中不存在。CaMKII γ的上调是否是消耗病理学的一部分，还是对萎缩的一些适应性反应的结果尚不清楚。未来的研究将是重要的，以确定是否从肌肉的适应性反应增加负荷的见解将提供药理学方法，增加肌肉力量或耐力，以对抗肌肉萎缩。
Intracellular Ca2+ plays an important role in skeletal muscle excitation-contraction coupling and also in excitation-transcription coupling. Activity-dependent alterations in muscle gene expression as a result of increased load (i.e. resistance or endurance training) or decreased activity (i.e. immobilization or injury) are tightly linked to the level of muscle excitation. Differential expression of genes in slow- and fast-twitch fibres is also dependent on fibre activation. Both these biological phenomena are, therefore, tightly linked to the amplitude and duration of the Ca2+ transient, a signal decoded downstream by Ca2+-dependent transcriptional pathways. Evidence is mounting that the calcineurin-nuclear factor of activated T-cells pathway and the Ca2+/calmodulin-dependent kinases (CaMK) 11 and IV play important roles in regulating oxidative enzyme expression, mitochondrial biogenesis and expression of fibre-type specific myofibrillar proteins. CaMKII is known to decode frequency-dependent information and is activated during hypertrophic growth and endurance adaptations. Thus, it was hypothesized that CaMKII, and possibly CaMKIV, are down regulated during muscle atrophy and levels of expression of CaMKIIalpha, -IIbeta, -IIgamma and -IV were assessed in skeletal muscles from young, aged and denervated rats. The results indicate that CaMKIIgamma, but not CaMKIIalpha or -beta, is up regulated in aged and denervated soleus muscle and that CaMKIV is absent in skeletal but not cardiac muscle. Whether CaMKIIgamma up-regulation is part of the pathology of wasting or a result of some adaptational response to atrophy is not known. Future studies will be important in determining whether insights from the adaptational response of muscle to increased loads will provide pharmacological approaches for increasing muscle strength or endurance to counter muscle wasting.