Effect of 2-deoxyglucose-mediated inhibition of glycolysis on the regulation of mTOR signaling and protein synthesis before and after high-intensity muscle contraction
Effect of 2-deoxyglucose-mediated inhibition of glycolysis on the regulation of mTOR signaling and protein synthesis before and after high-intensity muscle contraction
复制标题
DOI：
10.1016/j.metabol.2020.154419
复制
发表时间：
2021-01-01
影响因子：
9.8
通讯作者：
Ogasawara, Riki
中科院分区：
文献类型：
--
作者：
Suginohara, Takeshi;Wakabayashi, Koki;Ogasawara, Riki
背景：糖酵解控制mTORC 1信号传导和蛋白质合成。在骨骼肌中，葡萄糖代谢随着运动/收缩强度和体积而增加，因此，高强度肌肉收缩（HiMC）如阻力运动促进糖酵解，包括葡萄糖摄取和糖原分解。然而，糖酵解是否调节HiMC诱导的mTORC 1活化和蛋白质合成的增加尚不清楚。方法：为了确定糖酵解是否调节基础和HiMC诱导的mTORC 1信号传导和蛋白质合成，我们采用2-脱氧葡萄糖（2-DG）抑制糖酵解，并使用经皮电刺激等距收缩Sprague道利大鼠的腓肠肌。结果：2-DG对糖酵解的抑制作用抑制了p70 S6 K和4 E-BP 1（mTORC 1的下游靶点）的基础磷酸化以及蛋白质合成（均P < 0.05），而不依赖于AMPK磷酸化。AMPK磷酸化在HiMC后0小时在HiMC后急剧增加，并且在媒介物和2-DG处理组中在HiMC后6小时恢复到基础水平。结论：虽然糖酵解参与了HiMC诱导的基础蛋白合成，但它同时调节基础和HiMC诱导的mTORC 1信号，可能在骨骼肌适应HiMC中发挥关键作用。(C)2020爱思唯尔公司All rights reserved.
Background: Glycolysis controls mTORC1 signaling and protein synthesis. In skeletal muscle, glucose metabolism increases with both exercise/contraction intensity and volume, and therefore, high-intensity muscle contraction (HiMC) such as resistance exercise facilitates glycolysis including glucose uptake and glycogen breakdown. However, it is unknown whether glycolysis regulates HiMC-induced mTORC1 activation and increase in protein synthesis.Methods: To determine whether glycolysis regulates basal and HiMC-induced mTORC1 signaling and protein synthesis, we employed 2-deoxyglucose (2-DG) to inhibit glycolysis and isometrically contracted the gastrocnemius muscle of Sprague Dawley rats using percutaneous electrical stimulation.Results: Inhibition of glycolysis by 2-DG inhibited basal phosphorylation of p70S6K and 4E-BP 1 (downstream targets of mTORC1) and protein synthesis (all P < 0.05) independent of AMPK phosphorylation. AMPK phosphorylation was comparably increased after HiMC at 0 h post HiMC and returned to basal levels 6 h post HiMC in both vehicle- and 2-DG-treated groups. Glycolysis inhibition attenuated muscle contraction-induced phosphorylation of 4E-BP1 at 6 h post HiMC (P < 0.05) but not p70S6K phosphorylati on and protein synthesis.Conclusion: Although glycolysis is involved in basal but not HiMC-induced muscle protein synthesis, it regulates both basal and HiMC-induced mTORC1 signaling, and may play key roles in skeletal muscle adaptation to HiMC. (C) 2020 Elsevier Inc. All rights reserved.