Mammalian hibernators undergo major behavioural, physiological and biochemical changes to survive hypothermia, ischaemia-reperfusion and finite fuel reserves during days or weeks of continuous torpor. During hibernation, the 13-lined ground squirrel (Ictidomys tridecemlineatus) undergoes a global suppression of energetically expensive processes such as transcription and translation, while selectively upregulating certain genes/proteins to mitigate torpor-related damage. Antioxidant defenses are critical for preventing damage caused by reactive oxygen species (ROS) during torpor and arousal, and Nrf2 is a critical regulator of these antioxidant genes. This study analysed the relative protein expression levels of Nrf2, KEAP1, small Mafs (MafF, MafK and MafG) and catalase and the regulation of Nrf2 transcription factors by post-translational modifications (PTMs) and protein-protein interactions with a negative regulator (KEAP1) during hibernation. It was found that a significant increase in MafK during late torpor predicated an increase in relative Nrf2 and catalase levels seen in arousal. Additionally, Nrf2-KEAP1 protein-protein interactions and Nrf2 PTMs, including serine phosphorylation and lysine acetylation, were responsive to cycles of torpor-arousal with peak responses occurring during arousal. These peaks seen during arousal correspond to a surge in oxygen consumption, which causes increased ROS production. Thus, these regulatory mechanisms could be important during hibernation because they provide mechanisms for mitigating the deleterious effects of oxidative stress by modifying Nrf2 expression and function in an energetically inexpensive manner.

中文翻译：

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调节 Nrf2 转录因子活性：揭示 13 线地松鼠冬眠期间抗氧化防御的调节机制

哺乳动物冬眠者会经历重大的行为、生理和生化变化，以在数天或数周的连续麻木中生存低温、缺血再灌注和有限的燃料储备。在冬眠期间，13 线地松鼠 ( Ictidomys tridecemlineatus) 对转录和翻译等耗能巨大的过程进行全局抑制，同时选择性地上调某些基因/蛋白质以减轻与麻木相关的损伤。抗氧化防御对于防止在麻木和觉醒期间由活性氧 (ROS) 造成的损伤至关重要，而 Nrf2 是这些抗氧化基因的关键调节剂。本研究分析了 Nrf2、KEAP1、小 Mafs（MafF、MafK 和 MafG）和过氧化氢酶的相对蛋白质表达水平，以及通过翻译后修饰 (PTM) 和蛋白质-蛋白质相互作用与负调节因子 (KEAP1) 对 Nrf2 转录因子的调节) 在冬眠期间。发现在迟发期间 MafK 的显着增加预示着觉醒中看到的相对 Nrf2 和过氧化氢酶水平的增加。此外，Nrf2-KEAP1 蛋白质-蛋白质相互作用和 Nrf2 PTM，包括丝氨酸磷酸化和赖氨酸乙酰化，对睡眠唤醒周期有反应，在唤醒期间出现峰值反应。在唤醒期间看到的这些峰值对应于耗氧量的激增，这会导致 ROS 产生增加。因此，这些调节机制在冬眠期间可能很重要，因为它们提供了通过以一种能量低廉的方式修改 Nrf2 表达和功能来减轻氧化应激有害影响的机制。这会导致 ROS 产生增加。因此，这些调节机制在冬眠期间可能很重要，因为它们提供了通过以一种能量低廉的方式修改 Nrf2 表达和功能来减轻氧化应激有害影响的机制。这会导致 ROS 产生增加。因此，这些调节机制在冬眠期间可能很重要，因为它们提供了通过以一种能量低廉的方式修改 Nrf2 表达和功能来减轻氧化应激有害影响的机制。