Affiliation:
1. Department of Pathology at the Affiliated Hospital of Guizhou Medical University Key Laboratory of Endemic and Ethnic Diseases (Guizhou Medical University) of the Ministry of Education Guiyang China
2. Department of Medical Science and Technology Guiyang Healthcare Vocational University Guiyang China
3. Key Laboratory of Endemic and Ethnic Diseases (Guizhou Medical University) of the Ministry of Education and Provincial Key Laboratory of Medical Molecular Biology Guiyang China
4. Department of Hepatobiliary Surgery Affiliated Hospital to Guizhou Medical University Guiyang China
Abstract
AbstractIntroductionFor investigating the mechanism of brain injury caused by chronic fluorosis, this study was designed to determine whether NRH:quinone oxidoreductase 2 (NQO2) can influence autophagic disruption and oxidative stress induced in the central nervous system exposed to a high level of fluoride.MethodsSprague–Dawley rats drank tap water containing different concentrations of fluoride for 3 or 6 months. SH‐SY5Y cells were either transfected with NQO2 RNA interference or treated with NQO2 inhibitor or activator and at the same time exposed to fluoride. The enrichment of gene signaling pathways related to autophagy was evaluated by Gene Set Enrichment Analysis; expressions of NQO2 and autophagy‐related protein 5 (ATG5), LC3‐II and p62, and mammalian target of rapamycin (mTOR) were quantified by Western‐blotting or fluorescent staining; and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) assayed biochemically and reactive oxygen species (ROS) detected by flow cytometry.ResultsIn the hippocampal CA3 region of rats exposed to high fluoride, the morphological characteristics of neurons were altered; the numbers of autophagosomes in the cytoplasm and the levels of NQO2 increased; the level of p‐mTOR was decreased, and the levels of ATG5, LC3‐II and p62 were elevated; and genes related to autophagy enriched. In vitro, in addition to similar changes in NQO2, p‐mTOR, ATG5, LC3 II, and p62, exposure of SH‐SY5Y cells to fluoride enhanced MDA and ROS contents and reduced SOD activity. Inhibition of NQO2 with RNAi or an inhibitor attenuated the disturbance of the autophagic flux and enhanced oxidative stress in these cells exposed to high fluoride.ConclusionOur findings indicate that NQO2 may be involved in regulating autophagy and oxidative stress and thereby exerts an impact on brain injury caused by chronic fluorosis.
Funder
National Natural Science Foundation of China
Subject
Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology
Cited by
7 articles.
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