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Functional analysis of muscle-specific protein, ARPP, expressed in the atrophic skeletal muscles

萎缩骨骼肌中表达的肌肉特异性蛋白 ARPP 的功能分析

基本信息

批准号：
17590353
负责人：
HIIYA Naoki
金额：
$ 2.24万
依托单位：
Oita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590353/
关键词：
ARPP Knock-out mouse skeletal muscle muscle differentiation muscle injury muscle regeneration

项目摘要

Recently, we identified a novel human protein, ankyrin-repeated protein with PEST and praline-rich region (ARPP). ARPP is characterized structurally by the presence of four ankyrin-repeated domains in its central portion. The amino acid sequence of ARPP is highly homologous with that of cardiac restricted ankyrin-repeated protein (CARP; 52%). We observed high expression levels of ARPP in skeletal muscle and the heart. ARPP was selectively expressed in type 1 myofibers of skeletal muscle and, therefore, ARPP-positive myofibers were arranged in a checkerboard-like pattern. In this study, we analyzed the function of ARPP in vivo by generating ARPP knock-out (KO) mouse. Our findings are as follows;1) Compared with normal mouse, ARPP KO mouse showed decreased exercise capacity for endurance training2) ARPP expression in the skeletal muscle was found to be induced by denervation for 10 weeks.3) ARPP expression in the disuse atrophic skeletal muscle induced by tail-suspension was significantly down-regulated.4) ARPP KO mouse showed distinct expression pattern of some genes expressed specifically in the nervous system as well as skeletal muscle specific genes.5) ARPP KO mouse showed much more severe muscle injury induced by injection of cardiotoxin and delayed clearance of necrotic tissue compared with normal mouseThese findings suggest that ARPP might be concerned with the induced expression of the several proteins acting as the procetive effects in the muscle performance, muscle injury and muscle regeneration.

最近，我们发现了一种新的人类蛋白，具有PEST和脯氨酸富区（ARPP）的锚蛋白重复蛋白。ARPP在结构上的特点是在其中心部分存在四个锚蛋白重复结构域。ARPP的氨基酸序列与心脏限制性锚蛋白重复蛋白（CARP, 52%）高度同源。我们观察到ARPP在骨骼肌和心脏中的高表达水平。ARPP在骨骼肌1型肌纤维中选择性表达，因此，ARPP阳性的肌纤维呈棋盘状排列。在本研究中，我们通过生成ARPP敲除（KO）小鼠来分析ARPP在体内的功能。我们的研究结果如下：1)与正常小鼠相比，ARPP KO小鼠耐力训练的运动能力下降。2)去神经支配10周后，骨骼肌中ARPP的表达被诱导。3)悬尾诱导的废用萎缩骨骼肌ARPP表达显著下调。4) ARPP KO小鼠在神经系统特异性表达的部分基因和骨骼肌特异性表达的基因有明显的表达模式。5)与正常小鼠相比，ARPP对心脏毒素诱导的肌肉损伤和坏死组织清除延迟明显加重，提示ARPP可能与诱导几种蛋白的表达有关，这些蛋白在肌肉性能、肌肉损伤和肌肉再生中起促进作用。