The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells

Junling Zhao; Hao Liu; Zhiwei Huang; Ruiming Yang; Liang Gong

doi:10.3389/fnmol.2022.824762

The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells

Front Mol Neurosci. 2022 Mar 11:15:824762. doi: 10.3389/fnmol.2022.824762. eCollection 2022.

Authors

Junling Zhao¹, Hao Liu¹, Zhiwei Huang¹, Ruiming Yang¹, Liang Gong¹

Affiliation

¹ Department of Otolaryngology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Abstract

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.

Keywords: D-JNKI-1; HEI-OC1; JNK; apoptosis; neomycin.