Noise induced changes in the expression of p38/MAPK signaling proteins in the sensory epithelium of the inner ear

• Published in: Journal of proteomics 2011-12, Vol.75 (2), p.410-424
• Main Authors: Jamesdaniel, Samson, Hu, Bohua, Kermany, Mohammad Habiby, Jiang, Haiyan, Ding, Dalian, Coling, Donald, Salvi, Richard
• Format: Article
• Language: English
• Subjects: adhesion; Animals; antibody microarrays; Auditory system; Bioinformatics; Biological and medical sciences; biosynthesis; Cell death; Cell membranes; Chinchilla; Chinchilla (Chinchillidae); chinchillas; Cochlea; correlation; Diverse techniques; E2F3; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; ears; emissions; epithelium; fas Receptor; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases; Fundamental and applied biological sciences. Psychology; gene expression regulation; Hair Cells, Auditory, Outer; hearing; Hearing loss; Hearing Loss, Noise-Induced; injuries; MAP kinase; Medical sciences; metabolism; microarray technology; Molecular and cellular biology; Noise; Noise-induced hearing loss; Non tumoral diseases; nuclear proteins; Nuclei; otoacoustic emissions; Otoacoustic Emissions, Spontaneous; Otorhinolaryngology. Stomatology; outer hair cells; p38 Mitogen-Activated Protein Kinases; p38-MAP kinase; pathology; Phosphorylation; physiology; physiopathology; protein synthesis; Proteomics; Rodentia; sensory epithelium; Signal transduction; Stress; Trauma
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2011.08.007

Noise exposure is a major cause of hearing loss. Classical methods of studying protein involvement have provided a basis for understanding signaling pathways that mediate hearing loss and damage repair but do not lend themselves to studying large networks of proteins that are likely to increase or decrease during noise trauma. To address this issue, antibody microarrays were used to quantify the very early changes in protein expression in three distinct regions of the chinchilla cochlea 2h after exposure to a 0.5–8kHz band of noise for 2h at 112dB SPL. The noise exposure caused significant functional impairment 2h post-exposure which only partially recovered. Distortion product otoacoustic emissions were abolished 2h after the exposure, but at 4weeks post-exposure, otoacoustic emissions were present, but still greatly depressed. Cochleograms obtained 4weeks post-exposure demonstrated significant loss of outer hair cells in the basal 60% of the cochlea corresponding to frequencies in the noise spectrum. A comparative analysis of the very early (2h post-exposure) noise-induced proteomic changes indicated that the sensory epithelium, lateral wall and modiolus differ in their biological response to noise. Bioinformatic analysis of the cochlear protein profile using “The Database for Annotation, Visualization and Integrated Discovery 2008” (DAVID — http://david.abcc. ncifcrf.gov) revealed the initiation of the cell death process in sensory epithelium and modiolus. An increase in Fas and phosphorylation of FAK and p38/MAPK in the sensory epithelium suggest that noise-induced stress signals at the cell membrane are transmitted to the nucleus by Fas and focal adhesion signaling through the p38/MAPK signaling pathway. Up-regulation of downstream nuclear proteins E2F3 and WSTF in immunoblots and microarrays along with their immunolocalization in the outer hair cells supported the pivotal role of p38/MAPK signaling in the mechanism underlying noise-induced hearing loss. [Display omitted] ► Noise-induced proteomic responses differ in three discrete regions of the inner ear. ► Noise exposure induced an apoptotic response in sensory epithelium and modiolus. ► p38/MAPK signaling has a pivotal role in mediating noise-induced hearing loss.