The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.
The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.
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DOI：
10.2527/jas.2012-5737
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发表时间：
2013-07
影响因子：
3.3
通讯作者：
Koohmaraie M
中科院分区：
文献类型：
--
作者：
Kemp CM;Oliver WT;Wheeler TL;Chishti AH;Koohmaraie M
肌原纤维蛋白周转是肌肉生长和退化的关键组成部分，需要蛋白水解酶来降解骨骼肌蛋白。本研究的目的是利用μ-calpain敲除（KO）小鼠与对照野生型（WT）小鼠比较，探讨calpain蛋白水解系统在肌肉生长发育中的作用，并评估沉默该基因对其他蛋白水解系统的后续影响。在生长的早期阶段，由于其他蛋白水解系统的上调，没有观察到基因型之间肌肉发育的差异。KO小鼠m-calpain蛋白丰度和活性显著高于对照组（P < 0.01）， caspase 3/7活性显著高于对照组（P < 0.05）。30周龄时，KO小鼠的蛋白质：DNA比（P < 0.05）和RNA:DNA比（P < 0.01）增加，蛋白质含量增加（P < 0.01），脂肪沉积减少（P < 0.05），快速收缩糖酵解肌纤维的大小和数量增加（P < 0.05），表明KO小鼠骨骼肌中蛋白质积累和维持能力增强。此外，成熟KO小鼠肌肉再生相关蛋白（神经细胞粘附分子和myoD）的表达均降低（P < 0.05和P < 0.01），表明肌肉再生较少，因此肌肉损伤较小。这些发现表明，蛋白质水解系统的协同作用，以确保肌肉蛋白质在体内的稳态。此外，这些数据有助于钙蛋白酶系统参与肌肉生长、发育和萎缩的重要性的现有证据。总的来说，这些数据表明，钙蛋白酶系统有机会促进骨骼肌的生长和/或恢复。
Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P < 0.01) and activity (P < 0.001), and greater caspase 3/7 activity (P < 0.05). At 30 wk of age, KO mice showed increased protein:DNA (P < 0.05) and RNA:DNA ratios (P < 0.01), greater protein content (P < 0.01) at the expense of lipid deposition (P < 0.05), and an increase in size and number of fast-twitch glycolytic muscle fibers (P < 0.05), suggesting that KO mice exhibit an increased capacity to accumulate and maintain protein in their skeletal muscle. Also, expression of proteins associated with muscle regeneration (neural cell adhesion molecule and myoD) were both reduced in the mature KO mice (P < 0.05 and P < 0.01, respectively), indicating less muscle regeneration and, therefore, less muscle damage. These findings indicate the concerted action of proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system’s involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.
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影响因子：
30.8
作者：
Horikawa, Y;Oda, N;Bell, GI
通讯作者：
Bell, GI
影响因子：
5.3
作者：
Azam, M;Andrabi, SS;Chishti, AH
通讯作者：
Chishti, AH
影响因子：
5.3
作者：
Kuchay, Shafi M.;Kim, Nayoung;Chishti, Athar H.
通讯作者：
Chishti, Athar H.
影响因子：
2.9
作者：
DAYTON, WR;GOLL, DE;REVILLE, WJ
通讯作者：
REVILLE, WJ
影响因子：
4.8
作者：
Neumar, RW;Xu, YA;Siman, R
通讯作者：
Siman, R