• Neuroscience · Dec 2023

    ATF5 Attenuates Low-magnesium-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress Via the Regulation of Mitochondrial Reactive Oxygen Species.

    • Cui Wang, Xiaoyi Wang, Yinyin Xie, Tingting Peng, Yongfeng Wang, Nan Li, Xiangbo Huang, Xiaomei Hu, and Nanchang Xie.
    • Department of Clinical Laboratory, the First Affiliated Hospital of Zhengzhou University; Key Clinical Laboratory of Henan Province, Zhengzhou, China.
    • Neuroscience. 2023 Dec 15; 535: 132213-22.

    AbstractMitochondrial stress and endoplasmic reticulum stress (ERS) are known to be closely linked. ATF5 is a key regulator of mitochondrial stress and is involved in ERS regulation. Previously, we used a seizure model to demonstrate that ATF5 regulates mitochondrial stress. However, whether ATF5 affects ERS in epilepsy models has yet to be elucidated. In the present study, we investigated the effects of ATF5 on low-magnesium-induced ERS and the potential mechanisms that underlie these effects. We found that lentiviral overexpression of ATF5 significantly improved low-magnesium-induced ERS, as confirmed by the reduced expression levels of GRP78, PERK, ATF4, and CHOP. In addition, ATF5 overexpression reduced reactive oxygen species (ROS) production and elevated superoxide dismutase (SOD) activity, thus demonstrating that ATF5 plays a key role in maintaining redox homeostasis. Furthermore, ATF5 overexpression rescued low-magnesium-induced neuronal apoptosis, as evidenced by the reduced expression levels of Cleaved-caspase-3 and Bax, and the restored levels of Bcl2. However, these effects were significantly eliminated by lentiviral transduction with ATF5 interference. In addition, treatment of neurons with the mitochondrial antioxidant mitoquinone attenuated the onset of oxidative stress caused by ATF5 interference, partially restored the effect on ERS, and rescued cells from apoptosis. Collectively, these data show that ATF5 attenuates low-magnesium-induced neuronal apoptosis by inhibiting ERS through preventing the accumulation of mitochondrial ROS.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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