Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity

Wang, Linjia and Zhu, Rongxin and Wang, Jiahui and Yu, Siwang and Wang, Jianxiong and Zhang, Ying (2020) Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity. Medicine & Science in Sports & Exercise, 52 (8). pp. 1719-1728. ISSN 0195-9131


Abstract

Introduction
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.

Methods
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.

Results
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.

Conclusion
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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 10 Sep 2020 05:40
Last Modified: 11 Sep 2020 03:22
Uncontrolled Keywords: Monocarboxylate Transporter 1; Lactate; Nrf2; Skeletal Muscle; Hypoxic Exercise; Sulforaphane
Fields of Research (2008): 11 Medical and Health Sciences > 1106 Human Movement and Sports Science > 110602 Exercise Physiology
Identification Number or DOI: https://doi.org/10.1249/MSS.0000000000002312
URI: http://eprints.usq.edu.au/id/eprint/39451

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