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

• DOI: 10.3389/fphar.2024.1462421
• Publication Date: 2025-01-30T06:27:04Z
• Authors: Fan Wang; Yue Xu; Yajie Wang; Qian Liu; Yanan Li; Weiwei Zhang; Huiming Nong; Junhong Zhang; Hao Zhao; Huaqian Yang; Lingchuan Guo; Jianfeng Li; Hong Li; Qianqian Yang
• Keywords: Spiral ganglion

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 (ER-phagy) receptor, plays an important part in dynamic remodelling of ER, mutation affects sensory and autonomic neurons. However whether FAM134B-mediated ER-phagy involved Cis-induced SGN damage or not unknown. The present study designed to determine FAM134B is expressed SGNs C57BL/6 mice and, if so, explore potential function vitro . Methods Middle turns neonatal murine cochleae were cultured treated with 30 μM Cis distribution morphological changes SGNs, colocalization ER segments lysosomes measured immunofluorescence (IF). Apoptosis TUNEL staining. expression proteins associated stress, apoptosis western blot. reactive oxygen specie (ROS) levels evaluated MitoSOX Red 2′,7′-Dchlorodihydrofluorescein diacetate (DCFH-DA) probe. Anc80- Fam134b shRNA used knockdown SGNs. Results We found cytoplasm especially fourth postnatal day mice. showed decreases number expression, as well increases ROS level, ER-phagy, after stimulus. Inhibiting increased aggravated damage, while opposite observed when activated. Additionally, co-treatment N-Acetyl-L-Cysteine (NAC), scavenger, alleviated apoptosis. What’s more, made more vulnerable cisplatin-induced injury. Discussion revealed pattern for time. Moreover, our work further verified protective mediated apoptosis, at least partially, correlated accumulation induction though detailed regulatory mechanism through needs much reveal.