1. Increased m 6 A modification of BDNF mRNA via FTO promotes neuronal apoptosis following aluminum-induced oxidative stress.
- Author
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Song J, Hao J, Lu Y, Ding X, Li M, and Xin Y
- Subjects
- Animals, Rats, RNA, Messenger metabolism, RNA, Messenger genetics, PC12 Cells, Male, Hippocampus drug effects, Hippocampus metabolism, Glucosides, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, Apoptosis drug effects, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO metabolism, Oxidative Stress drug effects, Aluminum toxicity, Neurons drug effects, Adenosine analogs & derivatives, Organometallic Compounds, Pyrones
- Abstract
N6-methyladenosine (m
6 A) RNA modification is a new epigenetic molecular mechanism involved in various biological or pathological processes. Exposure to aluminum (Al) has been considered to promote neuronal apoptosis resulting in cognitive dysfunction, yet whether m6 A modification participates in the underlying mechanism remains largely unknown. Here, rats exposed to aluminum-maltolate [Al(mal)3 ] for 90 days showed impaired learning and memory function and elevated apoptosis, which were related to the increased m6 A level and decreased fat mass and obesity-associated protein (FTO, an m6 A demethylase) in the hippocampus. Accordingly, similar results presented in PC12 cells following Al(mal)3 treatment and FTO overexpression relieved the increased apoptosis and m6 A level in vitro. Next, we identified brain-derived neurotrophic factor (BDNF) as the functional downstream target of FTO in a m6 A-dependent manner. Furthermore, it was found that as the onset of aluminum neurotoxicity, oxidative stress may be the upstream regulator of FTO in aluminum-induced apoptosis. Taken together, these results suggest that increased m6 A modification of BDNF mRNA via FTO promotes neuronal apoptosis following aluminum-induced oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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