FAM134B-mediated endoplasmic reticulum autophagy protects against cisplatin-induced spiral ganglion neuron damage

作者：Fan Wang, Yue Xu, Yajie Wang, Qian Liu, Yanan Li, Weiwei Zhang, Huiming Nong, Junhong Zhang, Hao Zhao, Hua-Qian Yang, Lingchuan Guo, Jianfeng Li, Hong Li, Qianqian Yang · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2024.1462421 · 被引用次数：5 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Cell death mechanisms and regulation

Introduction Cochlear spiral ganglion neurons (SGNs) could be damaged by ototoxic drug, cisplatin (Cis), during which process autophagy was involved. FAM134B, the first detected endoplasmic reticulum autophagy (ER-phagy) receptor, plays an important part in the dynamic remodelling of the ER, the mutation of which affects sensory and autonomic neurons. However whether FAM134B-mediated ER-phagy involved in Cis-induced SGN damage or not was unknown. The present study was designed to determine whether FAM134B is expressed in SGNs of C57BL/6 mice and, if so, to explore the potential function of FAM134B in Cis-induced SGN damage in vitro . Methods Middle turns of neonatal murine cochleae were cultured and treated with 30 μM Cis in vitro . The distribution of FAM134B, morphological changes of SGNs, and the colocalization of ER segments with lysosomes were measured by immunofluorescence (IF). Apoptosis was measured by TUNEL staining. The expression of FAM134B, proteins associated with ER stress, autophagy and apoptosis was measured by western blot. The reactive oxygen specie (ROS) levels were evaluated by MitoSOX Red and 2′,7′-Dchlorodihydrofluorescein diacetate (DCFH-DA) probe. Anc80- Fam134b shRNA was used to knockdown the expression of FAM134B in SGNs. Results We first found the expression of FAM134B in the cytoplasm of SGNs, especially in the fourth postnatal day mice. Results showed decreases in the number of SGNs and FAM134B expression, as well as increases of ROS level, ER str...