Zhao Junling, Liu Hao, Huang Zhiwei, Yang Ruiming, Gong Liang
Department of Otolaryngology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Front Mol Neurosci. 2022 Mar 11;15:824762. doi: 10.3389/fnmol.2022.824762. eCollection 2022.
Aminoglycosides can cause ototoxicity and lead to hair cell damage. Neomycin-induced ototoxicity is related to increased production of reactive oxygen species (ROS) and triggering hair cell apoptosis. The c-Jun-N-terminal kinase (JNK) pathway plays an essential role during hair cell damage. This study was designed to investigate an inhibitor of JNK, D-JNKI-1 (AM-111/brimapitide) in neomycin-induced HEI-OC1 cell apoptosis. The results demonstrate that neomycin increased intracellular ROS accumulation, which induces apoptosis. D-JNKI-1 decreased neomycin-induced ROS generation, reduced caspase-8 and cleavage of caspase-3 expression, sustained JNK activation and AMPK and p38 phosphorylation, downregulated Bax, and upregulated Bcl-2. Together, D-JNKI-1 plays an essential role in protecting against neomycin-induced HEI-OC1 cell apoptosis by suppressing ROS generation, which inhibited JNK activation and AMPK and p38 phosphorylation to ameliorate JNK-mediated HEI-OC1 cell apoptosis.
氨基糖苷类药物可导致耳毒性并引起毛细胞损伤。新霉素诱导的耳毒性与活性氧（ROS）生成增加以及引发毛细胞凋亡有关。c-Jun氨基末端激酶（JNK）通路在毛细胞损伤过程中起重要作用。本研究旨在探讨JNK抑制剂D-JNKI-1（AM-111/布瑞米肽）对新霉素诱导的HEI-OC1细胞凋亡的影响。结果表明，新霉素增加细胞内ROS积累，进而诱导凋亡。D-JNKI-1减少新霉素诱导的ROS生成，降低半胱天冬酶-8表达及半胱天冬酶-3的切割，维持JNK激活以及AMPK和p38磷酸化，下调Bax并上调Bcl-2。总之，D-JNKI-1通过抑制ROS生成在预防新霉素诱导的HEI-OC1细胞凋亡中起重要作用，其抑制JNK激活以及AMPK和p38磷酸化以改善JNK介导的HEI-OC1细胞凋亡。
