Calcitriol alleviates noise-induced hearing loss by regulating the ATF3/DUSP1 signalling pathway.
Ecotoxicol Environ Saf
; 284: 116906, 2024 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-39182283
ABSTRACT
BACKGROUND:
Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea.METHODS:
C57BL/6â¯J mice were given six intraperitoneal injections of Cal (500â¯ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100⯵M tert-butyl hydroperoxide (TBHP) for 2.5â¯h and HEI-OC1 cells with 250⯵M TBHP for 1.5â¯h.RESULTS:
In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1â¯h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database ï¼GTRDï¼and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1.CONCLUSION:
The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Calcitriol
/
Transdução de Sinais
/
Estresse Oxidativo
/
Fator 3 Ativador da Transcrição
/
Fosfatase 1 de Especificidade Dupla
/
Perda Auditiva Provocada por Ruído
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article