NRF2/HO-1 pathway activation by ATF3 in a noise-induced hearing loss murine model.
Arch Biochem Biophys
; 721: 109190, 2022 05 30.
Article
em En
| MEDLINE
| ID: mdl-35331713
ABSTRACT
BACKGROUND:
Excessive oxidative stress of the inner ear as a result of high, intense noise exposure is regarded as a major mechanism underlying the development of noise-induced hearing loss (NIHL). The present study was designed to explore the effect and mechanism of activated transcription factor 3 (ATF3) in reduction/oxidation homeostasis of NIHL.METHOD:
In vitro and in vivo assays were performed to investigate the functional role of ATF3 in the inner ear. Mice hearing was measured using auditory brainstem response. ATF3 short hairpin RNA (shRNA) was transfected into House Ear Institute-Organ of Corti 1 (HEI-OC1) cells to decrease ATF3 expression. Western blotting and quantitative real-time polymerase chain reaction (RT-qPCR) were performed to quantify ATF3, NRF2, HO-1 and NQO1 expression. Glutathione (GSH) assay was performed to detect intracellular GSH levels. ATF3 immunofluorescence analysis was carried out in cochlear cryosectioned samples and HEI-OC1 cells to localize ATF3 expression. Cell counting kit 8 assay and flow cytometry were performed to analyze cell viability.RESULT:
ATF3 was upregulated in noise-exposed cochleae and HEI-OC1 cells treated with H2O2. NRF2 is a key factor regulated by ATF3. NRF2, HO-1, NQO1, and GSH expression was significantly downregulated in shATF3 HEI-OC1 cells. ATF3 silencing promoted reactive oxygen species accumulation and increased apoptosis and necrosis with H2O2 stimulus.CONCLUSION:
ATF3 functions as an antioxidative factor by activating the NRF2/HO-1 pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator 3 Ativador da Transcrição
/
Fator 2 Relacionado a NF-E2
/
Perda Auditiva Provocada por Ruído
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article