School of Sport Science, Beijing Sport University, Beijing, CHINA.
Shanghai Research Institute of Sports Science, Shanghai, CHINA.
Med Sci Sports Exerc. 2020 Aug;52(8):1719-1728. doi: 10.1249/MSS.0000000000002312.
Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate-pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle.
In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated.
The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline-exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN.
These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.
骨骼肌是乳酸产生和代谢的主要场所。单羧酸转运蛋白（MCT）蛋白家族，特别是 MCT1 和 MCT4，参与了乳酸-丙酮酸的交换和代谢。核因子红细胞 2 相关因子 2（Nrf2）是抗氧化反应和能量代谢的关键协调因子，据报道与骨骼肌的生理功能有关。
在这项研究中，C57BL/6 J 小鼠在缺氧下进行递增跑步机运动至力竭之前，给予 Nrf2 激活剂萝卜硫素（SFN）；然后评估 SFN 对运动耐力和骨骼肌分子/生化标志物的影响。
结果表明，SFN 预处理可增强缺氧下的运动耐力。SFN 不仅增加了抗氧化基因的表达和抗氧化酶的活性，而且还显著增加了 MCT1 和 CD147 的 mRNA 和蛋白水平，但 MCT4 没有增加。此外，SFN 运动组的 LDH-B 表达和将乳酸转化为丙酮酸的 LDH 活性以及柠檬酸合酶活性显著升高，而将丙酮酸转化为乳酸的 LDH 活性和血乳酸水平则明显低于磷酸盐缓冲盐水运动组。此外，运动进一步增加了 Atf3Δzip2（激活转录因子 3 的选择性剪接异构体）mRNA 的表达，而 SFN 则进一步增强了 Atf3Δzip2 的表达。
这些结果首次表明，SFN 在急性缺氧运动下增加了骨骼肌中的 MCT1 表达，并表明 Nrf2 激活是增强缺氧下运动表现的一种有前途的策略。
