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Early gene expression in the organ of Corti exposed to gentamicin
Ivana Nagy1, Morana Bodmer, Dominik Brors
1Clinic for Otolaryngology, Head & Neck Surgery, University Hospital Zurich, Frauenklinikstr. 24, 8091 Zurich, Switzerland.
Abstract:
Studies have demonstrated different pathogenetic key factors in gentamicin-induced hair cell death. The production of reactive oxygen species (ROS), as well as apoptosis-related genes, play a critical role. However, a coordinated large-scale investigation of gene expression in the organ of Corti (OC) exposed to gentamicin has not yet been conducted. Here we used DNA microarray technology to compare the expression profile of OC exposed to gentamicin to the expression profile of untreated OC. The OCs of Sprague Dawley rats were dissected and the basal turns were cultured. Two-thirds of the explants were then exposed to l00 microM gentamicin, for 4 and 8 h, while one-third of the explants remained in culture medium alone. Gene expression was analyzed using DNA microarray technology and the dChip software package. Based on the results, the 4-h time-point was chosen for further analysis. In these assays, out of 8800 genes, 12 genes were identified on the basis of differential expression in the OC exposed to gentamicin vs. control OC. The identity of these genes suggests that the response of the OC to the gentamicin challenge involves down-regulation of specific gene families in order to alleviate ROS and N-methyl-D-aspartate (NMDA) receptor-mediated cellular stress.
Insights
Gentamicin exposure triggers reactive oxygen species (ROS) and apoptosis, leading to hair cell death. This study identified 12 differentially expressed genes in the organ of Corti, revealing a protective down-regulation mechanism against cellular stress.
Area of Science:
- Ototoxicity research
- Molecular biology
- Auditory neuroscience
Background:
- Gentamicin is a known ototoxic antibiotic causing hair cell death.
- Reactive oxygen species (ROS) and apoptosis are implicated in gentamicin-induced ototoxicity.
- A comprehensive gene expression analysis in the organ of Corti (OC) following gentamicin exposure was lacking.
Purpose of the Study:
- To investigate the global gene expression profile of the organ of Corti (OC) after gentamicin exposure using DNA microarray technology.
- To identify specific genes and pathways involved in the cellular response to gentamicin.
- To understand the molecular mechanisms underlying gentamicin-induced hair cell damage.
Main Methods:
- Organ of Corti (OC) explants from Sprague Dawley rats were cultured.
- Explants were exposed to 100 microM gentamicin for 4 and 8 hours.
- Gene expression analysis was performed using DNA microarray technology and dChip software.
Main Results:
- Out of 8800 genes analyzed, 12 genes showed differential expression in gentamicin-treated OC compared to controls at the 4-hour time point.
- The identified genes suggest a cellular response involving the down-regulation of specific gene families.
- This down-regulation appears to be a protective mechanism against reactive oxygen species (ROS) and N-methyl-D-aspartate (NMDA) receptor-mediated stress.
Conclusions:
- Gentamicin exposure induces significant changes in gene expression within the organ of Corti.
- The down-regulation of specific genes is a key component of the cellular defense against gentamicin-induced stress.
- These findings provide insights into the molecular pathways involved in ototoxicity and potential targets for therapeutic intervention.
