关键词: BMAL1 Exercise timing NRF2-mediated antioxidant responses skeletal muscle

来  源:   DOI:10.1080/10715762.2024.2348789

Abstract:
It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.
摘要:
众所周知,肌肉抗氧化系统对有氧运动的适应取决于频率,强度,持续时间,练习的类型。尽管如此,有氧运动的时机,与昼夜节律或生物钟有关,也可能影响抗氧化防御系统,但其影响仍不确定。贝恩和肌肉ARNT-like1(BMAL1)是分子钟的核心协调器,它可以通过直接控制核因子红系2相关因子2(NRF2)的转录活性来维持细胞的氧化还原稳态。所以,我们的研究目的是评估每天不同时间点的有氧运动训练对骨骼肌中BMAL1和NRF2介导的抗氧化系统的影响.C57BL/6J小鼠被分配到对照组,在ZeitgeberTime12(ZT12)锻炼的小组,以及在ZT24锻炼的小组。对照小鼠未进行干预,虽然ZT12和ZT24小鼠在其活动期的早期和晚期时间点进行了四周的训练,分别。我们观察到,与ZT24小鼠相比,ZT12小鼠的骨骼肌表现出更高的总抗氧化能力和更低的活性氧。此外,ZT12小鼠改善了BMAL1与细胞核的共定位,与ZT24小鼠相比,BMAL1,NRF2,NAD(P)H醌氧化还原酶1,血红素加氧酶1,谷氨酸-半胱氨酸连接酶修饰亚基和谷胱甘肽还原酶的蛋白表达。总之,在ZT12进行的4周有氧训练对于增强NRF2介导的骨骼肌抗氧化反应更有效,这可能归因于BMAL1的特异性激活。
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