Lysine suppresses myofibrillar protein degradation by regulating the autophagic-lysosomal system through phosphorylation of Akt in C2C12 cells.

Lysine suppresses myofibrillar protein degradation by regulating the autophagic-lysosomal system through phosphorylation of Akt in C2C12 cells.
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DOI:
10.1186/2193-1801-3-584
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发表时间:
2014
期刊:
影响因子:
--
通讯作者:
Nagasawa T
Nagasawa T
中科院分区:
其他
文献类型:
--
作者:
Sato T;Ito Y;Nagasawa T

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预防肌肉萎缩对维持生活质量很重要,因为肌肉质量的损失会导致卧床不起和对疾病的抵抗力下降。预防肌肉萎缩需要增加骨骼肌中蛋白质的合成和减少蛋白质的降解。我们以前表明,赖氨酸(Lys)显着抑制肌原纤维蛋白降解通过抑制自噬溶酶体系统通过哺乳动物雷帕霉素靶(mTOR)和其他信号分子在C2 C12细胞。本研究探讨了自噬调节因子Akt和5′-磷酸腺苷(AMP)激活的蛋白激酶(AMPK)在赖氨酸抑制C2 C12细胞肌原纤维蛋白降解中的作用。Akt 1/2激酶抑制剂(Akt 1/2 kinase inhibitor,Akt 1/2 kinase inhibitor赖氨酸抑制AMPK的磷酸化,但这种作用也被Akti消除。另一方面,5-氨基咪唑-4-甲酰胺-1-β-D-核糖核苷(AICAR)激活AMPK并不影响Lys处理的C2 C12细胞中Akt活性或自噬-溶酶体系统。这些结果表明,AMPK活性的调节是不是必不可少的调节自噬的赖氨酸。总之,我们的研究结果表明,赖氨酸抑制肌原纤维蛋白降解的自噬溶酶体系统通过磷酸化Akt在C2 C12细胞。
The prevention of muscle wasting is important for maintaining quality of life, since loss of muscle mass can lead to a bedridden state and decreased resistance to diseases. The prevention of muscle wasting requires an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. We previously showed that lysine (Lys) markedly suppressed myofibrillar protein degradation by inhibiting the autophagic-lysosomal system via the mammalian target of rapamycin (mTOR) and other signal molecules in C2C12 cells. In this study, we investigated the involvement of Akt and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), two regulators of autophagy, on the suppressive effects of Lys on myofibrillar protein degradation in C2C12 cells. Lys induced the phosphorylation of Akt, but the suppressive effects of Lys on myofibrillar protein degradation and autophagy were completely abolished in the presence of Akt1/2 kinase inhibitor (Akti). Lys suppressed the phosphorylation of AMPK, but this effect was also abolished by Akti. On the other hand, AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) did not affect either Akt activity or the autophagic-lysosomal system in C2C12 cells treated with Lys. These results indicate that regulation of AMPK activity is not essential for the regulation of autophagy by Lys. Taken together, our results show that Lys suppresses myofibrillar protein degradation by the autophagic-lysosomal system through the phosphorylation of Akt in C2C12 cells.
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