Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats
Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats
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DOI：
10.1155/2020/6181630
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发表时间：
2020-02-15
影响因子：
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通讯作者：
Lin, Laixiang
中科院分区：
文献类型：
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作者：
Li, Yongmei;Zhang, Yuan;Lin, Laixiang
睡眠不足会对消化系统产生不良影响。多项研究表明，睡眠剥夺和氧化应激密切相关。自噬可以由氧化应激触发，作为促进生存的自我防御策略。在这项研究中，我们研究了睡眠剥夺对肝功能，氧化应激和伴随的肝细胞自噬的影响，以及相关的途径。采用血清酶和非酶生化指标评价肝功能和肝功能损害。为了评估自噬的发生，测试自噬相关蛋白的表达并标记自噬体。此外，使用化学方法和蛋白质印迹分析甲烷二羧酸醛（MDA）、抗氧化酶和蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。血清谷丙转氨酶、谷草转氨酶和碱性磷酸酶在睡眠剥夺大鼠中升高。总蛋白和白蛋白丰度也异常。睡眠剥夺引起肝脏的组织病理学变化。睡眠剥夺大鼠肝脏超氧化物歧化酶水平显著降低。而睡眠剥夺组MDA含量明显升高。此外，微管相关蛋白1轻链3 β（LC 3B）II/I比率和Beclin I含量在睡眠剥夺大鼠中显著增加，而p62水平降低。睡眠剥夺明显抑制AKT/mTOR信号通路。我们的结论是，睡眠剥夺可以诱导氧化应激，并最终导致肝损伤。氧化应激引发的自噬似乎是由AKT/mTOR通路介导的，并在缓解睡眠剥夺引起的氧化应激中发挥作用。
Sleep deprivation adversely affects the digestive system. Multiple studies have suggested sleep deprivation and oxidative stress are closely related. Autophagy can be triggered by oxidative stress as a self-defense strategy to promote survival. In this study, we investigated the effects of sleep deprivation on liver functions, oxidative stress, and concomitant hepatocyte autophagy, as well as the associated pathways. Enzymatic and nonenzymatic biochemical markers in the serum were used to assess hepatic function and damage. To evaluate the occurrence of autophagy, expression of autophagy-related proteins was tested and autophagosomes were labeled. Additionally, methane dicarboxylic aldehyde (MDA), antioxidant enzymes, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed using chemical methods and a Western blot. Serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase increased in sleep-deprived rats. Total protein and albumin abundance was also abnormal. Sleep deprivation induced histopathological changes in the liver. The superoxide dismutase level decreased significantly in the liver of sleep-deprived rats. In contrast, the MDA content increased in the sleep deprivation group. Moreover, the microtubule-associated protein 1 light chain 3 beta (LC3B) II/I ratio and Beclin I content increased considerably in the sleep-deprived rats, while p62 levels decreased. Sleep deprivation apparently inhibited the AKT/mTOR signaling pathway. We conclude that sleep deprivation can induce oxidative stress and ultimately cause liver injury. Autophagy triggered by oxidative stress appears to be mediated by the AKT/mTOR pathway and plays a role in relieving oxidative stress caused by sleep deprivation.