{
  "abstract": "Aminoglycoside-induced hearing loss is closely associated with oxidative stress and mitochondrial dysfunction in cochlear hair cells, but the upstream epigenetic mechanisms remain incompletely understood. This study investigated whether histone deacetylase 1 (HDAC1) contributes to neomycin-induced cochlear injury through transcriptional repression of NRF2. In HEI-OC1 cells, neomycin increased apoptosis, reactive oxygen species accumulation, mitochondrial depolarization, and mitochondrial superoxide production, accompanied by HDAC1 upregulation and NRF2 suppression. HDAC1 silencing attenuated these alterations and restored NRF2 expression. ChIP-qPCR demonstrated increased HDAC1 occupancy and reduced H3K27ac enrichment at the proximal NRF2 promoter after neomycin exposure, whereas HDAC1 knockdown reversed these changes. Consistently, HDAC1 silencing increased NRF2 promoter activity, while HDAC1 overexpression further suppressed NRF2 transcription and reduced H3K27ac levels. HDAC1 knockdown also restored nuclear NRF2 abundance and increased the downstream antioxidant proteins HO-1 and NQO1. Importantly, NRF2 overexpression partially rescued the reductions in cell viability and ATP content caused by HDAC1 overexpression, supporting a functional role for NRF2 downstream of HDAC1. In vivo, valproic acid partially preserved auditory thresholds, reduced cochlear hair cell apoptosis, restored NRF2 expression, and ameliorated mitochondrial ultrastructural damage in neomycin-treated mice. Collectively, these findings identify HDAC1-associated H3K27ac remodeling at the NRF2 promoter as an epigenetic mechanism contributing to neomycin-induced cochlear hair cell injury and support HDAC1-NRF2 regulation as a potential target for otoprotection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otorhinolaryngology-Head and Neck Surgery, The First People's Hospital of Yunnan Province, Kunming, 650034, Yunnan, China.",
    "The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.",
    "Department of Otorhinolaryngology, The People's Hospital of Yunxian, 22 Jianshe Road, Caopi Street Community, Aihua Town, Yunxian, Lincang, 675800, Yunnan, China.",
    "Department of Otorhinolaryngology-Head and Neck Surgery, The First People's Hospital of Yunnan Province, Kunming, 650034, Yunnan, China. 13987158566@163.com.",
    "The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, Yunnan, China. 13987158566@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "ShunMin Gong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "XianBao Cao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ling Jia"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "ShiFen Li"
    },
    {
      "affs": [
        2
      ],
      "name": "WenJu Cha"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "SiXuan Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dvndztfs8mxsy.bib",
  "cited_by": 0,
  "doi": "10.1007/s11064-026-04912-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13668915",
  "id": "dvndztfs8mxsy",
  "issns": [
    "0364-3190",
    "1573-6903"
  ],
  "landing_url": "https://europepmc.org/article/MED/42873335",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Hearing, Cochlea, Tinnitus, Genetics"
    ]
  ],
  "openalex": "W7221827836",
  "pdf_url": "https://europepmc.org/articles/PMC13668915?pdf=render",
  "pmcid": "PMC13668915",
  "pmid": "42873335",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dvndztfs8mxsy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42873335",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42873335"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Hearing, Cochlea, Tinnitus, Genetics",
      "subfield": "neuroscience"
    }
  ],
  "title": "HDAC1 Represses NRF2 Transcription via H3K27ac Remodeling to Aggravate Neomycin-Induced Cochlear Hair Cell Damage.",
  "title_text": "HDAC1 Represses NRF2 Transcription via H3K27ac Remodeling to Aggravate Neomycin-Induced Cochlear Hair Cell Damage.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/dvndztfs8mxsy",
  "venue": "Neurochemical research",
  "versions": []
}