{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:30:12Z","timestamp":1784683812149,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010086","name":"Foundation of Liaoning Province Education Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010086","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fnmol.2022.824762","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T10:04:58Z","timestamp":1646993098000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Junling","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1523\/ENEURO.0047-16.2016","article-title":"c-Jun N-Terminal Phosphorylation: biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea.","volume":"3","author":"Anttonen","year":"2016","journal-title":"eNeuro"},{"key":"B2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.2337\/diabetes.50.1.77","article-title":"Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death.","volume":"50","author":"Bonny","year":"2001","journal-title":"Diabetes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.cmet.2015.05.005","article-title":"Beyond energy homeostasis: the expanding role of AMP-activated protein kinase in regulating metabolism.","volume":"21","author":"Carling","year":"2015","journal-title":"Cell Metab."},{"key":"B4","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1196\/annals.1338.022","article-title":"Mitochondrial dysfunction and oxidative stress as determinants of cell death\/survival in stroke.","volume":"1042","author":"Chan","year":"2005","journal-title":"Ann. 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