Sphingosine 1-phosphate inhibits cell migration in C2C12 myoblasts
Sphingosine 1-phosphate inhibits cell migration in C2C12 myoblasts
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DOI：
10.1016/j.bbalip.2006.01.006
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发表时间：
2006-01-01
影响因子：
4.8
通讯作者：
Bruni, P
中科院分区：
文献类型：
--
作者：
Becciolini, L;Meacci, E;Bruni, P
这项研究表明，1-磷酸鞘氨醇（S1 P）通过降低定向细胞运动性和完全消除对胰岛素样生长因子-1的趋化反应，在C2 C12成肌细胞中发挥所有抗迁移作用。对S1 P的抗迁移反应需要与S1 P（2）连接，在成肌细胞中被特异性反义寡脱氧核糖核苷酸或小干扰RNA（siRNA）下调的受体减弱，相反在S1 P（2）过度表达的成肌细胞中增强。RhoA和Rac GTPases的研究表明，RhoA被S1 P迅速激活，而Rac 1在前5分钟内不受影响，但此后受到刺激。RhoA，而不是Rac激活，在通过siRNA处理减弱受体表达或通过S1 P（2）编码质粒转染上调受体表达的实验中被鉴定为S1 P（2）依赖性途径。最后，通过表达RhoA的显性负突变体，发现GTdR与S1 P的抗迁移作用有关，而Rac 1功能的调节不影响S1 P的抗趋化作用，排除了这种蛋白质在生物反应中的作用。由于S1 P先前显示出抑制成肌细胞增殖并刺激肌生成，因此此处鉴定的新生物活性有利于鞘脂在肌肉修复过程中的复杂生理作用。(c)2006 Elsevier B. V.保留所有权利。
This study shows that sphingosine 1-phosphate (S1P) exerts ail anti-migratory action in C2C12 myoblasts by reducing directional cell motility and fully abrogating the chemotactic response to insulin-like growth factor-1. The anti-migratory response to S1P required ligation to S1P(2), being attenuated in myoblasts where the receptor was down-regulated by specific antisense oligodeoxyribonucleotides or small interfering RNA (siRNA) and conversely potentiated in S1P(2)-overexpressing myoblasts. The investigation of RhoA and Rac GTPases, critically implicated in cell motility regulation, demonstrated that RhoA was rapidly activated by S1P, while Rac1 was unaffected within the first 5 min but stimulated thereafter. RhoA, but not Rac activation, was identified as a S1P(2)-dependent pathway in experiments in which receptor expression was attenuated by siRNA treatment or up-regulated by S1P(2)-encoding plasmid transfection. Finally, by expression of the dominant negative mutant of RhoA, the GTPase was found implicated in the anti-migratory action of S1P, whereas modulation of Rac1 functionality unaffected the antichemotactic effect of S1P, ruling out a role for this protein in the biological response. Since S1P was previously shown to inhibit myoblast proliferation and stimulate myogenesis, the here identified novel biological activity is in favour of a complex physiological role of the sphingolipid in the process of muscle repair. (c) 2006 Elsevier B.V. All rights reserved.