Department of Physical Therapy, College of Public Health & Welfare, Yongin University, Yongin 449-714, Korea.
Korean J Physiol Pharmacol. 2009 Dec;13(6):491-6. doi: 10.4196/kjpp.2009.13.6.491. Epub 2009 Dec 31.
Skeletal muscle atrophy is a common phenomenon during the prolonged muscle disuse caused by cast immobilization, extended aging states, bed rest, space flight, or other factors. However, the cellular mechanisms of the atrophic process are poorly understood. In this study, we investigated the involvement of mitogen-activated protein kinase (MAPK) in the expression of muscle-specific RING finger 1 (MuRF1) during atrophy of the rat gastrocnemius muscle. Histological analysis revealed that cast immobilization induced the atrophy of the gastrocnemius muscle, with diminution of muscle weight and cross-sectional area after 14 days. Cast immobilization significantly elevated the expression of MuRF1 and the phosphorylation of p38 MAPK. The starvation of L6 rat skeletal myoblasts under serum-free conditions induced the phosphorylation of p38 MAPK and the characteristics typical of cast-immobilized gastrocnemius muscle. The expression of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly attenuated by SB203580, an inhibitor of p38 MAPK. Changes in the sizes of L6 myoblasts in response to starvation were also reversed by their transfection with MuRF1 small interfering RNA or treatment with SB203580. From these results, we suggest that the expression of MuRF1 in cast-immobilized atrophy is regulated by p38 MAPK in rat gastrocnemius muscles.
骨骼肌萎缩是由石膏固定、老龄化状态延长、卧床休息、太空飞行或其他因素导致的肌肉长期失用引起的一种常见现象。然而，萎缩过程的细胞机制还知之甚少。在这项研究中，我们研究了丝裂原活化蛋白激酶（MAPK）在大鼠比目鱼肌萎缩过程中肌肉特异性环指蛋白 1（MuRF1）表达中的作用。组织学分析表明，石膏固定导致比目鱼肌萎缩，14 天后肌肉重量和横截面积减小。石膏固定显著增加了 MuRF1 的表达和 p38 MAPK 的磷酸化。在无血清条件下培养 L6 大鼠骨骼肌成肌细胞可诱导 p38 MAPK 的磷酸化以及与石膏固定比目鱼肌相似的特征。血清饥饿也可使 L6 成肌细胞中 MuRF1 的表达升高，但 p38 MAPK 的抑制剂 SB203580 可显著抑制其表达。MuRF1 小干扰 RNA 转染或 SB203580 处理可逆转 L6 成肌细胞对饥饿的大小变化。从这些结果我们可以得出结论，在大鼠比目鱼肌中，石膏固定引起的 MuRF1 表达受 p38 MAPK 调节。
