ARC protects cochlear hair cells from neomycin-induced ototoxicity via the Ras/JNK signaling pathway.

The present study was designed to investigate the role and mechanism of the Apoptosis repressor with caspase recruitment domain (ARC) in protecting the neomycin-induced hair cell damage. HEI-OC1 cells and basilar membrane culture were applied to determine the effect of ARC. Plasmid transfection was used to regulate the ARC or Ras expression. We have found the ARC overexpression in HEI-OC1 cells can increase the cell viability and decrease cell apoptosis after neomycin injury. The cleaved caspase 3 was reduced in ARC overexpression group after neomycin treatment. The p-CREB expression was increased in ARC overexpression group, while the p-c-Jun expression was decreased after neomycin incubation. In HEI-OC1 cells and basilar membranes, JNK and Ras inhibitions both can reduce ARC expression, and Ras overexpression can increase the ARC expression. This study indicates that ARC can protect the hair cells from neomycin-induced apoptosis through Ras/JNK signaling pathway. Our findings provide new insights in preventing cochlear HC death after drug-induced ototoxicity.