Inhibition of DHCR24 increases the cisplatin-induced damage to cochlear hair cells in vitro.
Neurosci Lett
; 706: 99-104, 2019 07 27.
Article
em En
| MEDLINE
| ID: mdl-31091460
ABSTRACT
Hearing loss is a common sensory disorder that affects more than 360 million people worldwide, and is primarily caused by the loss of hair cells (HCs). Ototoxic drugs, viral infections, genetic predisposition, aging or noise all damage HCs. 3ß-hydroxysteroid-Δ24 reductase (DHCR24), one enzyme in the cholesterol biosynthetic pathway, is involved in inï¬ammation, oxidative stress and neuroprotection. However, researchers have not determined whether DHCR24 is present in the cochlea and the mechanism by which it exerts its regulatory effect on HC loss. In the present study, we analyzed DHCR24 expression in the postnatal day 1 (P1) rat cochlea and found that DHCR24 was localized in HCs of the organ of Corti. Next, exposure to cisplatin caused HC loss in cochlear organotypic cultures. Then, we inhibited DHCR24 expression with U18666A and observed significantly increased cisplatin-induced damage of cochlear HCs. These findings were consistent with the observed increase in DHCR24 expression in response to cisplatin treatment, and U18666A significantly decreased DHCR24 expression. Finally, DHCR24 inhibition increased the levels of reactive oxygen species and cleaved caspase-3 after cisplatin-induced injury. Collectively, DHCR24 may play a significant role in regulating auditory function and potentially represents a new therapeutic target for the treatment of cisplatin-induced ototoxicity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
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Agentes_cancerigenos
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
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Oxirredutases atuantes sobre Doadores de Grupo CH-CH
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Células Ciliadas Auditivas
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Proteínas do Tecido Nervoso
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Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China