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Diacylglycerol kinase η regulates C2C12 myoblast proliferation through the mTOR signaling pathway.
Biochimie ( IF 3.3 ) Pub Date : 2020-08-11 , DOI: 10.1016/j.biochi.2020.07.018
Hiromichi Sakai 1 , Chiaki Murakami 2 , Takako Usuki 2 , Qiang Lu 2 , Ken-Ichi Matsumoto 1 , Takeshi Urano 3 , Fumio Sakane 2
Affiliation  

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol to produce phosphatidic acid (PA). The η isozyme of DGK is abundantly expressed in C2C12 myoblasts. However, the role of DGKη in skeletal muscle cells remains unknown. In the present study, we showed that DGKη was downregulated at an early stage of myogenic differentiation. The knockdown of DGKη by siRNAs significantly inhibited C2C12 myoblast proliferation but did not inhibit differentiation. Moreover, the suppression of DGKη expression decreased the expression levels of mammalian target of rapamycin (mTOR), which is a key regulator of cell proliferation, and fatty acid synthase (FASN), which catalyzes the de novo synthesis of fatty acids for cell proliferation and is transcriptionally regulated via mTOR signaling. Furthermore, the knockdown of mTOR or raptor, which is a component of mTOR complex 1 (mTORC1), decreased the amount of FASN. These results indicate that DGKη regulates myoblast proliferation through the mTOR (mTORC1)-FASN pathway. Interestingly, the knockdown of mTOR reduced the expression levels of DGKη, implying mutual regulation between DGKη and mTOR. In DGKη-knockdown myoblasts, C30–C36-PA species, mTOR activators, were decreased, suggesting that the modulation of mTOR activity through these PA species also plays an important role in myoblast proliferation.



中文翻译:

二酰基甘油激酶η通过mTOR信号通路调节C2C12成肌细胞增殖。

二酰基甘油激酶(DGK)使二酰基甘油磷酸化,生成磷脂酸(PA)。DGK的η同工酶在C2C12成肌细胞中大量表达。然而,DGKη在骨骼肌细胞中的作用仍然未知。在本研究中,我们表明DGKη在成肌分化的早期被下调。siRNA抑制DGKη可以显着抑制C2C12成肌细胞增殖,但不抑制分化。此外,抑制DGKη的表达降低了哺乳动物雷帕霉素靶标(mTOR)和脂肪酸合酶(FASN)的表达水平,雷帕霉素是细胞增殖的关键调节剂,而脂肪酸合酶则催化从头脂肪酸合成用于细胞增殖,并通过mTOR信号传导进行转录调控。此外,作为mTOR复合物1(mTORC1)的组成部分的mTOR或猛禽的敲低降低了FASN的量。这些结果表明DGKη通过mTOR(mTORC1)-FASN途径调节成肌细胞增殖。有趣的是,mTOR的敲低降低了DGKη的表达水平,这暗示了DGKη和mTOR之间的相互调节。在DGKn抑制型成肌细胞中,mTOR活化剂C30–C36-PA种类减少,表明通过这些PA种类对mTOR活性的调节在成肌细胞增殖中也起重要作用。

更新日期:2020-08-16
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