Increased expression of δCaMKII isoforms in skeletal muscle regeneration:: Implications in dystrophic muscle disease
Increased expression of δCaMKII isoforms in skeletal muscle regeneration:: Implications in dystrophic muscle disease
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DOI：
10.1002/jcb.20669
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发表时间：
2006-02-15
影响因子：
4
通讯作者：
Shaw, C
中科院分区：
文献类型：
--
作者：
Abraham, ST;Shaw, C
钙-钙调蛋白/依赖性蛋白激酶11（CaMKII）的8种亚型的表达已被报道在哺乳动物骨骼肌中，然而，它们在该组织中的功能在很大程度上是未知的。进行本研究以确定在两种不同模型中骨骼肌纤维再生期间δ CaMKII表达是否改变。在第一个模型中，通过肌肉注射50%甘油在正常小鼠的四头肌中诱导坏死和再生。免疫染色和共聚焦显微镜显示，三角洲CaMKII的表达明显增强纤维显示集中的核。第二个模型是mdx小鼠，由于肌营养不良蛋白基因突变，其经历增强的肌肉坏死和再生。4 - 6周龄mdx小鼠的后腿提取物的血清印迹分析显示，与年龄匹配的对照小鼠相比，Δ CaMK II含量降低。在肌原纤维和膜组分中观察到6激酶含量的这种损失，并且与营养不良小鼠的心脏和脑提取物中未改变的δ CaMKII水平形成对比。mdx股四头肌和胫骨肌的共聚焦显微镜显示，在营养不良小鼠的大多数纤维中，delta CaMKII表达均匀减少;然而，在再生肌纤维中观察到激酶表达增强。这些数据支持δ CaMKII在正常和mdx骨骼肌肌纤维再生过程中的基本作用，并可能在肌肉死亡后的修复过程中具有重要意义。
The expression of 8 isoforms of calcium-calmodulin/dependent protein kinase 11 (CaMKII) has been reported in mammalian skeletal muscle; however, their functions in this tissue are largely unknown. This study was conducted to determine if delta CaMKII expression was altered during regeneration of skeletal muscle fibers in two distinct models. In the first model, necrosis and regeneration were induced in quadriceps of normal mice by intramuscular administration of 50% glycerol. Immunostaining and confocal microscopy revealed that delta CaMKII expression was clearly enhanced in fibers showing centralized nuclei. The second model was the mdx Mouse, which undergoes enhanced muscle necrosis and regeneration due to a mutation in the dystrophin gene. sern blot analysis of hind leg extracts from 4 to 6 week old mdx mice revealed that delta CaMKII content was decreased when compared to age-matched control mice. This loss in 6 kinase content was seen in myofibrillar and membrane fractions and was in contrast to unchanged delta CaMKII levels in cardiac and brain extracts from dystrophic mice. Confocal microscopy of mdx quadriceps and tibialis muscle showed that delta CaMKII expression was uniformly decreased in most fibers from dystrophic mice; however, enhanced kinase expression was observed in regenerating muscle fibers. These data Support a fundamental role for delta CaMKII in the regeneration process Of Muscle fibers in normal and mdx skeletal muscle and may have important implications in the reparative process following muscle death.