NRF2/HO-1 pathway activation by ATF3 in a noise-induced hearing loss murine model

Wang，Xiaodi1; Zeng，Chenghui1; Lai，Yanbing1; Su，Bo1; Chen，Fangyi2,3; Zhong，Jinhao2; Chu，Hanqi1; Bing，Dan1

2022-05-30

10.1016/j.abb.2022.109190

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   影响因子和分区

0003-9861

1096-0384

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 HO. 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 HO stimulus. Conclusion: ATF3 functions as an antioxidative factor by activating the NRF2/HO-1 pathway.

ATF3 NIHL NRF2 NRF2/HO-1 pathway Oxidation

SCI

英语

其他

China Postdoctoral Science Foundation[2017M613326];Li Ka Shing Foundation[2020LKSFG13C];Shenzhen-Hong Kong Institute of Brain Science[2021SHIBS0002];National Natural Science Foundation of China[81500794];National Natural Science Foundation of China[81771004];Shenzhen Fundamental Research Program[JCYJ20170817104949999];Shenzhen Science and Technology Innovation Program[JSGG20200225151916021];

Biochemistry & Molecular Biology ; Biophysics

Biochemistry & Molecular Biology ; Biophysics

WOS:000790514400003

ELSEVIER SCIENCE INC

BIOLOGY & BIOCHEMISTRY

2-s2.0-85126864121

Scopus

1.Department of Otorhinolaryngology Head and Neck Surgery,Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei,China
2.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China
3.Department of Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen,518055,China

Wang，Xiaodi,Zeng，Chenghui,Lai，Yanbing,et al. NRF2/HO-1 pathway activation by ATF3 in a noise-induced hearing loss murine model[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,2022,721.

Wang，Xiaodi.,Zeng，Chenghui.,Lai，Yanbing.,Su，Bo.,Chen，Fangyi.,...&Bing，Dan.(2022).NRF2/HO-1 pathway activation by ATF3 in a noise-induced hearing loss murine model.ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,721.

Wang，Xiaodi,et al."NRF2/HO-1 pathway activation by ATF3 in a noise-induced hearing loss murine model".ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 721(2022).