Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells
Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells
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DOI：
10.1091/mbc.e06-05-0402
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发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Graziani, Andrea
中科院分区：
文献类型：
--
作者：
Filigheddu, Nicoletta;Gnocchi, Viola F.;Graziani, Andrea
Ghrelin是一种酰化肽基胃激素，作用于垂体和下丘脑，通过激活生长激素促分泌素受体（GHSR）-1a受体刺激食欲、肥胖和生长激素释放。此外，生长素释放肽具有几种活性，例如抑制细胞凋亡、调节分化以及刺激或抑制几种细胞类型的增殖。Ghrelin酰化是GHSR-1a结合及其中枢内分泌活动所必需的。然而，不结合GHSR-1a且缺乏任何内分泌活性的未酰化的生长素释放肽形式脱酰基生长素释放肽在血浆中比生长素释放肽丰富得多，并且其与生长素释放肽共享其一些细胞活性。因此，我们发现生长素释放肽和去酰基生长素释放肽在体外通过激活p38刺激增殖C2 C12骨骼肌成肌细胞分化和融合成多核肌管。因此，生长素释放肽和去酰基生长素释放肽都抑制生长培养基中的C2 C12增殖。此外，Ghrelin在C2 C12中的异位表达增强了这些成肌细胞在分化培养基中的分化和融合。最后，我们表明，C2 C12细胞不表达GHSR-1a，但它们确实含有一个共同的高亲和力结合位点，由酰化和去酰化生长激素释放肽识别，这表明所描述的C2 C12活动可能是由这种新的，但尚未确定的受体两种生长激素释放肽形式介导的。
Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. inhere we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.