CATEGORY:
Research
TITLE:
Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network
DESCRIPTION:
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that…
CONTENT:
Cell Rep. 2020 Nov 24;33(8):108431. doi: 10.1016/j.celrep.2020.108431.
ABSTRACT
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that a subset of the genes encoding these proteins also increases acutely after noise exposure, including numerous proteasome subunits. Global cochlear protein ubiquitylation levels build up after exposure to excess noise, and we map numerous posttranslationally modified lysines residues. Several collagen proteins decrease in abundance, and Col9a1 specifically localizes to pillar cell heads. After two weeks of recovery, the cochlea selectively elevates the abundance of the protein synthesis machinery. We report that overstimulation of the auditory system drives a robust cochlear proteotoxic stress response.
PMID:33238128 | DOI:10.1016/j.celrep.2020.108431
SOURCE:
Cell reports
DATE – PUBLISHED:
24 Nov 2020
DATE – ADDED:
Wed, 25 Nov 2020 06:00:00 -0500
DATE – FOUND:
11/26/20 05:57AM
PUBMED ID:
pubmed:33238128
DOI:
10.1016/j.celrep.2020.108431
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33238128/
DOI LINK:
https://doi.org/10.1016/j.celrep.2020.108431
PUBLISHER LINK:
https://linkinghub.elsevier.com/retrieve/pii/S2211124720314200
JOURNAL LINK:
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31420-0