The role of peroxiredoxin III in the ototoxic drug-induced mitochondrial apoptosis of cochlear hair cells.

Abstract

CONCLUSION: Peroxiredoxin (Prx) III plays a protective role in cisplatin- and gentamicin-induced apoptosis via a mitochondria-dependent pathway in cochlear hair cells.

OBJECTIVES: The aim of the present study was to investigate the effects of the depletion of endogenous Prx III on oxidative damage to mitochondrial components and on apoptotic events with the use of RNA interference.

MATERIALS AND METHOD: . Depletion of Prx III was done by RNA interference in cochlear hair cells (UB/OC-1), and cells were exposed to ototoxic drugs (cisplatin or gentamicin). We then compared the apoptotic signaling between Prx III-depleted and control cells.

RESULTS: The depletion of Prx III resulted in increased intracellular ROS levels accompanied by enhanced apoptosis by ototoxic drugs. The Prx III-depleted cells showed mitochondrial membrane potential collapse, cytochrome c release, and caspase activation.