TMT-Based Quantitative Proteomics Reveals Cochlear Protein Profile Alterations in Mice with Noise-Induced Hearing Loss

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2022 Jan 11

PMID 35010640

Authors

Long Miao

Juan Zhang

Lihong Yin

Yuepu Pu

Affiliations

Soon will be listed here.

Abstract

Noise-induced hearing loss (NIHL) is a global occupational disease affecting health. To date, genetic polymorphism studies on NIHL have been performed extensively. However, the proteomic profiles in the cochleae of mice suffering noise damage remain unclear. The goal of this current study was to perform a comprehensive investigation on characterizing protein expression changes in the cochlea based on a mouse model of NIHL using tandem mass tag (TMT)-labeling quantitative proteomics, and to reveal the potential biomarkers and pathogenesis of NIHL. Male C57BL/6J mice were exposed to noise at 120 dB SPL for 4 h to construct the NIHL mouse model. The levels of MDA and SOD, and the production of proinflammatory cytokines including TNF-α and IL-6 in the mice cochleae, were determined using chemical colorimetrical and ELISA kits. Moreover, differentially expressed proteins (DEPs) were validated using Western blotting. The mouse model showed that the ABR thresholds at frequencies of 4, 8, 12, 16, 24 and 32 kHz were significantly increased, and outer hair cells (HCs) showed a distinct loss in the noise-exposed mice. Proteomics analysis revealed that 221 DEPs were associated with NIHL. Bioinformatics analysis showed that a set of key inflammation and autophagy-related DEPs (ITGA1, KNG1, CFI, FGF1, AKT2 and ATG5) were enriched in PI3K/AKT, ECM-receptor interaction, and focal adhesion pathways. The results revealed that the MDA level was significantly increased, but the activity of SOD decreased in noise-exposed mice compared to the control mice. Moreover, TNF-α and IL-6 were significantly increased in the noise-exposed mice. Western blotting revealed that the expression levels of ITGA1, KNG1, and CFI were upregulated, but FGF1, AKT2, and ATG5 were significantly downregulated in noise-exposed mice. This study provides new scientific clues about the future biomarkers and pathogenesis studies underlying NIHL. Furthermore, the findings suggest that the validated DEPs may be valuable biomarkers of NIHL, and inflammation and autophagy may be pivotal mechanisms that underlie NIHL.

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