ArticleThe Journal of biological chemistry2012
Cisplatin-induced ototoxicity is mediated by nitroxidative modification of cochlear proteins characterized by nitration of Lmo4.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- MnTBAP, a peroxynitrite scavenger, attenuates cisplatin-induced apoptosis and cytotoxicity in organ of Corti cells.Toxicology reports · 2025Article
- Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells.Current research in toxicology · 2025Article
- Quantitative profiling of cochlear synaptosomal proteins in cisplatin-induced synaptic dysfunction.Hearing research · 2024Article
- Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure.Cell stress · 2024Article
- Molecular Characteristics of Cisplatin-Induced Ototoxicity and Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Article
- Nitrative Stress and Auditory Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Lead exposure induces nitrative stress and disrupts ribbon synapses in the cochlea.Frontiers in molecular neuroscience · 2022Article
- Oxidative Stress and Inflammation Caused by Cisplatin Ototoxicity.Antioxidants (Basel, Switzerland) · 2021Review
- Lmo4 Deficiency Enhances Susceptibility to Cisplatin-Induced Cochlear Apoptosis and Hearing Loss.Molecular neurobiology · 2021Article
- Cisplatin-induced hair cell loss in zebrafish neuromasts is accompanied by protein nitration and Lmo4 degradation.Toxicology and applied pharmacology · 2021Article
- Ototoxicity in patients with invasive ductal breast cancer who were treated with docetaxel: report of two cases.Cancer biology & therapy · 2020Article
- Strategies to reduce the risk of platinum containing antineoplastic drug-induced ototoxicity.Expert opinion on drug metabolism & toxicology · 2020Review
- Current Strategies to Combat Cisplatin-Induced Ototoxicity.Frontiers in pharmacology · 2020Review
- Inhibition of protein nitration prevents cisplatin-induced inactivation of STAT3 and promotes anti-apoptotic signaling in organ of Corti cells.Experimental cell research · 2019Article
- CRISPR/Cas9-mediated knockout of Lim-domain only four retards organ of Corti cell growth.Journal of cellular biochemistry · 2018Article
- A Glycine-Rich RNA-Binding Protein, CsGR-RBP3, Is Involved in Defense Responses Against Cold Stress in Harvested Cucumber (Frontiers in plant science · 2018Article
- The impact of erdosteine on cisplatin-induced ototoxicity: a proteomics approach.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2017Article
- Proteomic Analysis of Differentially Accumulated Proteins in Cucumber (Frontiers in plant science · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Tyrosine nitration is an important sequel of cellular signaling induced by reactive oxygen species. Cisplatin is an anti-neoplastic agent that damages the inner ear through reactive oxygen species and by the formation of DNA adducts. This study reveals a correlation between cisplatin-mediated hearing loss and nitroxidative modification of cochlear proteins and is the first to report nitration of Lmo4. Cisplatin induced a dose-dependent increase in hearing loss in Wistar rats. A 10-15-dB decrease in distortion product amplitude and massive loss of outer hair cells at the basal turn of the cochlea was observed 3 days post-treatment after a 16 mg/kg dose. Cisplatin induced nitration of cellular proteins within the organ of Corti, spiral ganglion, and stria vascularis, which are known targets of cisplatin ototoxicity. Nitration of a 76-kDa cochlear protein correlated with cisplatin dose. The nitrated protein was identified as Lmo4 (LIM domain only 4) by MALDI-TOF (matrix-assisted laser desorption/ionization time of flight) mass spectrometry and confirmed by reciprocal immunoprecipitation and immunoblotting. Co-localization of nitrotyrosine and Lmo4 was particularly high in outer hair cell nuclei after cisplatin treatment. Cochlear levels of Lmo4 were decreased in rats treated with cisplatin. In vitro studies supported the repression of Lmo4 in nitroxidative conditions and the induction of apoptosis upon repression of Lmo4. Inhibition of cochlear protein nitration prevented cisplatin-induced hearing loss. As Lmo4 is a transcriptional regulator that controls the choice between cell survival and cell death, these results support the hypothesis that nitration of Lmo4 influences cisplatin-induced ototoxicity.
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