Identification of Target Proteins Involved in Cochlear Hair Cell Progenitor Cytotoxicity following Gentamicin Exposure.

Abstract

Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.