β-Hydroxy-β-methyl Butyrate Is More Potent Than Leucine in Inhibiting Starvation-Induced Protein Degradation in C2C12 Myotubes
β-Hydroxy-β-methyl Butyrate Is More Potent Than Leucine in Inhibiting Starvation-Induced Protein Degradation in C2C12 Myotubes
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DOI：
10.1021/acs.jafc.7b04841
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发表时间：
2018-01-10
影响因子：
6.1
通讯作者：
Yin, Yulong
中科院分区：
文献类型：
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作者：
Duan, Yehui;Li, Fengna;Yin, Yulong
亮氨酸（Leu）及其代谢产物α -酮异己酸酯（KIC）和β -羟基- β -丁酸甲酯（HMB）是蛋白质周转的有效调节剂。本研究的目的是比较亮氨酸、KIC和HMB对蛋白质降解的抑制作用，并探讨其机制。结果表明，HMB（0.38 +/- 0.04）的抑制作用强于Leu（0.76 +/- 0.04）和KIC (0.56 +/- 0.04, P < 0.01), LY294002（1.48 +/- 0.02）和雷帕霉素（1.96 +/- 0.02,P < 0.01）的抑制作用显著减弱。在胰岛素存在的情况下，HMB（0.34 +/- 0.03）的抑制作用仍优于Leu（0.60 +/- 0.04）和KIC （0.57 +/- 0.08, P < 0.05）。有趣的是，LY294002治疗明显减弱了HMB的作用，而雷帕霉素治疗没有起到同样的作用。因此，无论胰岛素是否存在，HMB在抑制蛋白质降解方面似乎比Leu和KIC更有效，并且这种抑制作用可能依赖于PI3K/Akt信号通路，而与胰岛素无关，mTOR信号通路仅参与HMB在缺乏胰岛素时的这种作用。
Leucine (Leu) and its metabolites alpha-ketoisocaproate (KIC) and beta-hydroxy-beta-methyl butyrate (HMB) are potent regulators of protein turnover. The aim of this study was to compare the inhibitory effects of Leu, KIC, and HMB on protein degradation and to investigate the mechanisms involved. The results showed that the inhibitory effect of HMB (0.38 +/- 0.04) was more potent than that of Leu (0.76 +/- 0.04) and KIC (0.56 +/- 0.04, P < 0.01), and was significantly abolished in the presence of LY294002 (1.48 +/- 0.02) and rapamycin (1.96 +/- 0.02, P < 0.01). In the presence of insulin, the inhibitory effect of HMB (0.34 +/- 0.03) was still more effective than that of Leu (0.60 +/- 0.04) and KIC (0.57 +/- 0.08, P < 0.05). Interestingly, LY294002 treatment markedly attenuated the effect of HMB, while rapamycin treatment failed to exert the same effect. Thus, HMB appears to be more potent than Leu and KIC in inhibiting protein degradation in the absence or presence of insulin, and this inhibitory effect may be dependent on PI3K/Akt signaling pathway regardless of insulin, and mTOR signaling was only involved in this effect of HMB in the absence of insulin.