Mechanism of Antigravity Muscle Atrophy

摘要大鼠比目鱼肌萎缩的特征是22kda蛋白的早期显著减少。这种蛋白质存在于肌肉的可溶性隔室和肌纤维z带中。该22 kda蛋白与牛晶状体α -结晶蛋白（alphaB-crystallin）的B链序列同源性为95%。从大鼠心脏cDNA文库中克隆了alphaB-Crystallin cDNA，确定了其完整编码区和部分非编码区DNA序列。制备了针对大鼠肌α -结晶蛋白的多克隆抗体。Northern分析和免疫印迹显示，α -结晶蛋白基因和蛋白在慢骨骼肌和心肌中表达，在快骨骼肌中表达水平较低。光镜和电镜下的免疫细胞化学显示，离体骨骼肌肌原纤维的z带中存在肌α -晶体蛋白。Northern分析显示，α -晶体蛋白基因表达抑制是诱发急性肌萎缩的早期事件之一。基于与晶状体α -晶体蛋白的序列同源性，初步确定了其功能作用，表明肌肉α -晶体蛋白是一种肌原纤维稳定蛋白，在肌肉萎缩的早期变化中受到转录调节。

Abstract Atrophy of rat soleus muscles is characterized by an early dramatic decrease in a 22-kDa protein. This protein is found in the soluble compartment of muscle and in the myofibrillar Z-band. The 22-kDa protein shows a 95% sequence homology with the B chain of bovine lens alpha-crystallin (alphaB-crystallin). alphaB-Crystallin cDNA was cloned from rat heart cDNA library and the DNA sequence for the complete coding region and for partial non-coding regions were determined. A polyclonal antibody was also produced to rat muscle alphaB-crystallin. Northern analysis and immunoblotting revealed alphaB-crystallin gene and protein expression in slow skeletal and cardiac muscle, and low levels of expression in fast skeletal muscle. Immunocytochemistry at the light and electron microscope levels revealed localization of muscle alphaB-crystallin in Z-bands of isolated myofibrils of skeletal muscles. Northern analysis revealed that alphaB-crystallin gene expression inhibition is one of the early events of induced acute muscular atrophy. Based upon sequence homology with lens alphaB-crystallin, a functional role is tentatively assigned suggesting that muscle alphaB-crystallin is a myofibril-stabilizing protein that is transcriptionally regulated during early changes in muscle atrophy.