Early transcriptional response to XXXX antibiotic suggests alternate pathways leading to apoptosis in sensory hair cells in the mouse inner ear.

@entity1 @entity801 @entity2167 @entity10062 @entity2348 @entity5292 @entity14032 @entity393
@entity5292 antibiotics are "the drug of choice" for treating many @entity2348 , but their administration results in @entity393 in up to one fourth of the @entity1 who receive them. Several biochemical pathways have been implicated in @entity5292 antibiotic @entity2167 ; however, little is known about how hair cells respond to @entity5292 antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the @entity5292 antibiotic @entity801 . Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from @entity10062 -purified hair cells. Within 3 h of @entity801 treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the @entity14032 pathway and the NF-kB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to @entity801 share a considerable similarity with those previously observed in @entity801 -induced nephrotoxicity. Our findings suggest that previously observed early responses to @entity801 in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternate pathway regulating @entity801 -induced apoptotic hair cell death. This work provides a more comprehensive view of @entity5292 antibiotic @entity2167 , and thus contributes to identifying potential pathways or therapeutic targets to alleviate this important side effect of @entity5292 antibiotics.
