Hibernators have evolved effective mechanisms to overcome the challenges of torpor-arousal cycling. This study focuses on the antioxidant and inflammatory defenses under the control of the redox-sensitive and inflammatory-centered NFκB transcription factor in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), a well-established model of mammalian hibernation. While hibernators significantly depress oxygen consumption and overall metabolic rate during torpor, arousal brings with it a rapid increase in respiration that is associated with an influx of reactive oxygen species. As such, hibernators employ a variety of antioxidant defenses to combat oxidative damage. Herein, we used Luminex multiplex technology to examine the expression of key proteins in the NFκB transcriptional network, including NFκB, super-repressor IκBα, upstream activators TNFR1 and FADD, and downstream target c-Myc. Transcription factor DNA-binding ELISAs were also used to measure the relative degree of NFκB binding to DNA during hibernation. Analyses were performed across eight different tissues, cerebral cortex, brainstem, white and brown adipose tissue, heart, liver, kidney, and spleen, during euthermic control and late torpor to highlight tissue-specific NFκB mediated cytoprotective responses against oxidative stress experienced during torpor-arousal. Our findings demonstrated brain-specific NFκB activation during torpor, with elevated levels of upstream activators, inactive-phosphorylated IκBα, active-phosphorylated NFκB, and enhanced NFκB-DNA binding. Protein levels of downstream protein, c-Myc, also increased in the brain and adipose tissues during late torpor. The results show that NFκB regulation might serve a critical neuroprotective and cytoprotective role in hibernating brains and selective peripheral tissue.

中文翻译：

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哺乳动物冬眠过程中NFκB通路调控的多组织特征。

冬眠者已经开发出了有效的机制来克服酷刑循环的挑战。这项研究的重点是在成熟的哺乳动物冬眠模型13里衬的地松鼠（Ictidomys tridecemlineatus）中，在氧化还原敏感和以炎症为中心的NFκB转录因子的控制下，抗氧化和防御炎症。尽管冬眠者显着降低了躯干过程中的耗氧量和总体代谢率，但唤醒引起呼吸的迅速增加，这与活性氧的涌入有关。因此，冬眠者采用各种抗氧化剂防御措施来抵抗氧化损伤。在这里，我们使用Luminex多重技术检查了NFκB转录网络中关键蛋白的表达，包括NFκB，超级阻遏物IκBα，上游激活因子TNFR1和FADD，以及下游目标c-Myc。转录因子DNA结合ELISA也用于测量休眠期间NFκB与DNA结合的相对程度。在正常的控制和后期的porpor中，对八种不同的组织（大脑皮层，脑干，白色和棕色脂肪组织，心脏，肝脏，肾脏和脾脏）进行了分析，以突出组织特异性NFκB介导的针对torpor-期间经历的氧化应激的细胞保护反应。唤起 我们的发现表明，在干烧过程中脑特异性NFκB活化，上游活化剂水平升高，非活性磷酸化IκBα，活性磷酸化NFκB和增强的NFκB-DNA结合。在后期玉米粥中，脑和脂肪组织中下游蛋白c-Myc的蛋白水平也增加。