Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats.

Abstract

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.