FAM134B Attenuates Seizure-Induced Apoptosis and Endoplasmic Reticulum Stress in Hippocampal Neurons by Promoting Autoph
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ORIGINAL RESEARCH
FAM134B Attenuates Seizure‑Induced Apoptosis and Endoplasmic Reticulum Stress in Hippocampal Neurons by Promoting Autophagy Nanchang Xie1 · Yingjiao Li1 · Cui Wang2 · Yajun Lian1 · Haifeng Zhang1 · Yujuan Li1 · Xianghe Meng1 · Liyuan Du1 Received: 16 December 2019 / Accepted: 14 February 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Autophagy plays a critical role in epileptic neuronal injury, and recent studies have demonstrated that FAM134B plays an important role in regulating autophagy. However, the effect of FAM134B on epileptic neuronal injury remains unclear. In this study, we investigated the role of FAM134B in neuronal apoptosis and endoplasmic reticulum (ER) stress using the hippocampal neuronal culture model of acquired epilepsy (AE) in vitro. We found that in this model, the level of autophagy significantly increased, indicated by an elevated LC3-II/LC3-I ratio. FAM134B overexpression using lentiviral vectors enhanced autophagy, whereas FAM134B downregulation using lentiviral vectors impaired this process. In addition, the ER Ca2+ concentration was decreased and the intracellular level of reactive oxygen species was increased in this model. FAM134B overexpression was sufficient to reverse these changes. Moreover, FAM134B overexpression attenuated ER stress as shown by a decrease in the expression of C/-EBP homologous protein and glucose-regulated protein 78, and neuronal apoptosis induced by seizure, while FAM134B downregulation caused the opposite effects. Further, pre-treatment with the selective autophagy inhibitor 3-methyladenine abolished the effects of FAM134B on ER stress and neuronal apoptosis. Altogether, we demonstrate that FAM134B is an important regulator of AE-induced ER stress and neuronal apoptosis by controlling autophagy function. Keywords FAM134B · Autophagy · Epilepsy · Endoplasmic reticulum stress · Apoptosis
Introduction Autophagy alterations exist in a variety of neurological diseases, including epilepsy (Giorgi et al. 2015). The Family with sequence similarity 134, member B (FAM134B), which contains a reticulon homology domain (RHD) and LC3-interacting region (LIR), is the firstly identified ER autophagy receptor and exerts an important effect on normal cell homeostasis by regulating autophagy (Islam et al. 2018). FAM134B controls ER turnover by specific binding to microtubule-associated protein 1 light chain 3B (MAP1LC3B), which in turn binds to the phagophore membrane via its C-terminal LC3-interacting region (LIR) (Bhaskara et al. 2019). Recent studies have demonstrated * Nanchang Xie [email protected] 1
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2
that FAM134B-regulated autophagy is crucial for cell survival, especially under conditions of stress (Khaminets et al. 2015). However, the role of FAM134B-regulated autophagy in epileptic neu
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