Structural and regulatory roles of muscle ankyrin repeat protein family in skeletal muscle
Structural and regulatory roles of muscle ankyrin repeat protein family in skeletal muscle
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DOI：
10.1152/ajpcell.00055.2007
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发表时间：
2007-07-01
影响因子：
5.5
通讯作者：
Lieber, Richard L.
中科院分区：
文献类型：
--
作者：
Barash, Ilona A.;Bang, Marie-Louise;Lieber, Richard L.
肌肉对偏心收缩（ECs）的生物反应可以加强和保护进一步的损伤。然而，这种反应的细胞基础尚不清楚。先前的研究发现，肌肉锚蛋白重复序列（MARP）家族，包括心脏锚蛋白重复序列（CARP）、锚蛋白重复结构域2/具有PEST和脯氨酸丰富区域的锚蛋白重复序列（Ankrd2/Arpp）和糖尿病相关锚蛋白重复序列（DARP），在小鼠单次EC后迅速特异性上调。为了确定这些基因在骨骼肌中的作用，研究人员对缺乏所有三种MARP家族成员（MKO）的小鼠进行了骨骼肌结构和功能特征调查。MKO肌肉纤维类型分布有较慢的趋势，但肌纤维大小没有差异。单个MKO纤维硬度较低，静息肌节长度较长，并且比野生型纤维表达的titin亚型更长，这表明这些蛋白质可能在肌肉的被动机械行为中发挥作用。最后，与野生型小鼠相比，MKO小鼠在一次ECs后表现出更大程度的扭矩损失，尽管它们从损伤中恢复的时间过程相同，甚至有所改善。这种恢复与肌肉调节基因MyoD和肌肉LIM蛋白（MLP）的表达增强有关，表明MARP家族可能在骨骼肌中发挥重要的结构和基因调节作用。
The biological response of muscle to eccentric contractions (ECs) results in strengthening and protection from further injury. However, the cellular basis for this response remains unclear. Previous studies identified the muscle ankyrin repeat protein (MARP) family, consisting of cardiac ankyrin repeat protein (CARP), ankyrin repeat domain 2/ankyrin repeat protein with PEST and proline-rich region (Ankrd2/Arpp), and diabetes-associated ankyrin repeat protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC. To determine the role of these genes in skeletal muscle, a survey of skeletal muscle structural and functional characteristics was performed on mice lacking all three MARP family members (MKO). There was a slight trend toward MKO muscles having a slower fiber type distribution but no differences in muscle fiber size. Single MKO fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that these proteins may play a role in the passive mechanical behavior of muscle. Finally, MKO mice showed a greater degree of torque loss after a bout of ECs compared with wild-type mice, although they recovered from the injury with the same or even improved time course. This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein (MLP), suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle.