Suppression of protein degradation by leucine requires its conversion to β-hydroxy-β-metnyl butyrate in C2C12 myotubes
Suppression of protein degradation by leucine requires its conversion to β-hydroxy-β-metnyl butyrate in C2C12 myotubes
复制标题
亮氨酸抑制蛋白质降解需要其在 C2C12 肌管中转化为 β-羟基-β-甲基丁酸盐
DOI：
10.18632/aging.102509
复制
发表时间：
2019-12-31
期刊：
影响因子：
5.2
通讯作者：
Li, Fengna
中科院分区：
文献类型：
--
作者：
Duan, Yehui;Zhong, Yinzhao;Li, Fengna
本研究旨在探讨亮氨酸（Leu）对饥饿诱导的蛋白质降解的抑制作用是否由其代谢产物β-羟基-β-甲基丁酸（HMB）介导，并探索相关机制。结果表明，亮氨酸对蛋白质降解和细胞耗氧率（OCR）的有益作用在低水平（0.5 mM）时可观察到，而在高水平（10 mM）时则未观察到。然而，这些作用不如HMB的作用显著。此外，HMB能够分别增加/降低肌球蛋白重链I（MyHC I）/肌球蛋白重链IIb（MyHC IIb）蛋白表达的比例。在这些转染了KICD的细胞中，亮氨酸在抑制蛋白质降解、增加细胞的OCR以及MyHC I蛋白表达方面与HMB大致同样有效，并且亮氨酸的这些作用可被KICD的特异性抑制剂甲基磺草酮恢复到正常状态。总之，在饥饿模型中，HMB似乎是亮氨酸抑制肌肉蛋白质降解的一种活性代谢产物，其机制可能与提高肌肉细胞的线粒体氧化能力有关。
The aims of this study were to investigate whether the inhibitory effect of Leucine (Leu) on starvation-induced protein degradation was mediated by its metabolite beta-hydroxy-beta-methyl butyrate (HMB), and to explore the mechanisms involved. The results showed that the beneficial effects of Leu on protein degradation and the oxygen consumption rate (OCR) of cells were observed at low levels (0.5 mM) rather than at high levels (10 mM). However, these effects were inferior to those of HMB. Moreover, HMB was able to increase/decrease the proportion of MyHC I/MyHC IIb protein expression, respectively. In these KICD-transfected cells, Leu was approximately as effective as HMB in inhibiting protein degradation and increasing the OCR as well as MyHC I protein expression of cells, and these effects of Leu were reverted to a normal state by mesotrione, a specific suppressor of KICD. In conclusion, HMB seems to be an active metabolite of Leu to suppress muscle protein degradation in a starvation model, and the mechanisms may be associated with improved mitochondrial oxidative capacity in muscle cells.