Overexpression of calpastatin inhibits L8 myoblast fusion
Overexpression of calpastatin inhibits L8 myoblast fusion
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DOI：
10.1016/j.bbrc.2005.05.010
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发表时间：
2005-07-08
影响因子：
3.1
通讯作者：
Kosower, NS
中科院分区：
文献类型：
--
作者：
Barnoy, S;Maki, M;Kosower, NS
骨骼肌纤维的形成涉及成肌细胞分裂的停止、成肌细胞排列和融合成多核肌纤维。钙蛋白酶是参与成肌细胞融合的因子之一。使用L 8大鼠成肌细胞，我们发现钙蛋白酶水平在成肌细胞分化过程中没有显著变化，而钙蛋白酶抑制蛋白在成肌细胞融合前减少，融合后重新出现。钙蛋白酶抑制蛋白的瞬时减少允许钙激活钙蛋白酶和钙蛋白酶诱导的膜蛋白水解，这是成肌细胞融合所需的。在这里，我们表明，钙蛋白酶抑制蛋白在L 8成肌细胞过表达不抑制细胞增殖和排列，但防止成肌细胞融合和融合相关蛋白降解。此外，钙蛋白酶抑制剂似乎调节肌原基因的表达，如在过表达钙蛋白酶抑制剂的成肌细胞中缺乏肌细胞生成素（一种在分化成肌细胞中表达的转录因子）所示。这些结果表明，除了在融合成肌细胞膜解体的作用，钙蛋白酶-钙蛋白酶抑制蛋白系统也可以调节成肌细胞分化所需的因子的水平。(c)2005年爱思唯尔公司All rights reserved.
The formation of skeletal muscle fibers involves cessation of myoblast division, myoblast alignment, and fusion to multinucleated myofibers. Calpain is one of the factors shown to be involved in myoblast fusion. Using L8 rat myoblasts, we found that calpain levels did not change significantly during myoblast differentiation, whereas calpastatin diminished prior to myoblast fusion and reappeared after fusion. The transient diminution in calpastatin allows the Ca2+-promoted activation of calpain and calpain-induced membrane proteolysis, which is required for myoblast fusion. Here we show that calpastatin overexpression in L8 myoblasts does not inhibit cell proliferation and alignment, but prevents myoblast fusion and fusion-associated protein degradation. In addition, calpastatin appears to modulate myogenic gene expression, as indicated by the lack of myogenin (a transcription factor expressed in differentiating myoblasts) in myoblasts overexpressing calpastatin. These results suggest that, in addition to the role in membrane disorganization in the fusing myoblasts, the calpain-calpastatin system may also modulate the levels of factors required for myoblast differentiation. (c) 2005 Elsevier Inc. All rights reserved.