Calcineurin-mediated slow-type fiber expression and growth in reloading condition
Calcineurin-mediated slow-type fiber expression and growth in reloading condition
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DOI：
10.1249/01.mss.0000222833.43520.6e
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发表时间：
2006-06-01
期刊：
影响因子：
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通讯作者：
Takemasa, Tohru
中科院分区：
文献类型：
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作者：
Miyazaki, Mitsunori;Hitomi, Yoshiaki;Takemasa, Tohru
目的：钙调神经磷酸酶(CaN)信号通路参与慢肌纤维基因的转录调控和肌肉肥大。我们的目的是研究在从静止状态恢复的条件下，CaN作为肌肉生长和/或肌肉纤维类型的调节因子的功能作用。方法：选用雌性ICR小鼠(8周龄，28~32g)。为了研究后肢悬吊和再负荷对骨骼肌纤维大小和肌纤维类型的影响，动物被指定为后肢悬吊8wk，然后再负荷4wk。在再负荷过程中，动物经腹腔注射CaN(FK506)药物抑制剂(3-5 mg·kg(-1)·d(-1))。在每个实验周期结束后，对反重力比目鱼肌进行分析。结果：HS治疗后比目鱼肌出现明显的肌萎缩和由慢向快的纤维型转化。HS后4wk的随后再负荷导致肌肉再生和纤维型回复到缓慢的轮廓。FK506可阻止这种再负荷诱导的肌纤维类型转化。此外，FK506的应用被证实减弱了纤维横截面积的维持和再负荷诱导的纤维再生，特别是在慢型肌肉纤维中。结论：CaN的药理抑制可阻止再负荷诱导的纤维型向慢速的逆转。此外，抑制CaN可阻止慢型肌肉纤维的维持和再生。这些结果表明，在维持和悬浮-再负荷条件下，慢型肌纤维程序需要CaN信号通路。
Purpose: Calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes and in muscle hypertrophy. Our aim was to investigate the functional role of CaN as a regulator of muscle growth and/or muscle fiber type under conditions of recovery from inactivity. Methods: Female ICR mice (8 wk of age, 28-32 g) were used. To examine the effects of hindlimb suspension (HS) and reloading on skeletal muscle fiber size and muscle fiber type, animals were designated to 8 wk of HS and subsequent reloading for 4 wk. During reloading, animals were treated with pharmacological inhibitors for CaN (FK506) by intraperitoneal administration (3-5 mg(.)kg(-1.)d(-1)). After each experimental period, anti gravitational soleus muscle was analyzed. Results: HS treatment resulted in obvious muscle atrophy and slow-to-fast fiber-type transformation in the soleus muscle. Subsequent reloading for 4 wk following HS induced muscle regrowth and fiber-type reversion toward a slow profile. FK506 administration prevented this kind of reloading-induced transformation of muscle fiber type. Furthermore, it was confirmed that FK506 administration attenuated maintenance of fiber cross-sectional area and reloading-induced fiber regrowth, specifically in slow-type muscle fibers. Conclusion: Reloading-induced fiber-type reversion toward a slow profile is prevented by the pharmacological inhibition of CaN. Additionally, inhibition of CaN prevented maintenance and regrowth of slow-type muscle fibers. These results implicate that the CaN signaling pathway is required in the slow-type muscle fiber program under maintenance and suspension-reloading conditions.