RRC ID 60024
著者 Hayward T, Young A, Jiang A, Crespi EJ, Coffin AB.
タイトル Glucococorticoid receptor activation exacerbates aminoglycoside-induced damage to the zebrafish lateral line.
ジャーナル Hear Res
Abstract Aminoglycoside antibiotics have potent antibacterial properties but cause hearing loss in up to 25% of patients. These drugs are commonly administered in patients with high glucocorticoid stress hormone levels and can be combined with exogenous glucocorticoid treatment. However, the interaction of stress and aminoglycoside-induced hearing loss has not been fully explored. In this study, we investigated the effect of the glucocorticoid stress hormone cortisol on hair cells in the zebrafish lateral line as an important step toward understanding how physiological stressors modulate hair cell survival. We found that 24-hr cortisol incubation sensitized hair cells to neomycin damage. Pharmacological and genetic manipulation demonstrates that sensitization depended on the action of the glucocorticoid receptor but not the mineralocorticoid receptor. Blocking endogenous cortisol production reduced hair cell susceptibility to neomycin, further evidence that glucocorticoids modulate aminoglycoside ototoxicity. Glucocorticoid transcriptional activity was apparent in lateral line hair cells, suggesting a direct action of cortisol in these aminoglycoside-sensitive cells. Our work shows that the stress hormone cortisol can increase hair cell sensitivity to aminoglycoside damage, which highlights the importance of recognizing stress and the impacts of glucocorticoid signaling in both ototoxicity research and clinical practice.
巻・号 377
ページ 12-23
公開日 2019-6-1
DOI 10.1016/j.heares.2019.03.002
PII S0378-5955(18)30356-3
PMID 30878773
MeSH Animals Anti-Bacterial Agents / toxicity* Gentamicins / toxicity* Glucocorticoids / toxicity* Hair Cells, Auditory / drug effects* Hair Cells, Auditory / metabolism Hair Cells, Auditory / pathology Hydrocortisone / toxicity* Lateral Line System / drug effects* Lateral Line System / embryology Lateral Line System / metabolism Neomycin / toxicity* Receptors, Glucocorticoid / agonists* Receptors, Glucocorticoid / genetics Receptors, Glucocorticoid / metabolism Signal Transduction Transcription, Genetic / drug effects Zebrafish / embryology Zebrafish Proteins / agonists* Zebrafish Proteins / genetics Zebrafish Proteins / metabolism
IF 2.952
引用数 0
リソース情報
ゼブラフィッシュ s357