Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 65, Issue 15, Pages 2407-2418Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-008-8195-y
Keywords
prestin; outer hair cell electromotility; salicylate; aspirin; functional dependence; hearing; tinnitus
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Funding
- NIDCD NIH HHS [R01 DC005989-03, R01 DC005989-04, DC 05989, R01 DC005989-02, R01 DC005989, R01 DC005989-01A2, R01 DC005989-05] Funding Source: Medline
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Salicylate (aspirin) can reversibly eliminate outer hair cell (OHC) electromotility to induce hearing loss. Prestin is the OHC electromotility motor protein. Here we report that, consistence with increase in distortion product otoacoustic emission, long-term administration of salicylate can increase prestin expression and OHC electromotility. The prestin expression at the mRNA and protein levels was increased by three- to four-fold. In contrast to the acute inhibition, the OHC electromotility associated charge density was also increased by 18%. This incremental increase was reversible. After cessation of salicylate administration, the prestin expression returned to normal. We also found that long-term administration of salicylate did not alter cyclooxygenase (Cox) II expression but down-regulated NF-kappa B and increased nuclear transcription factors c-fos and egr-1. The data suggest that prestin expression in vivo is dynamically up-regulated to increase OHC electromotility in long-term administration of salicylate via the Cox-II-independent pathways.
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