Hair Cell Protection from Ototoxic Drugs

Figure 1

AGs and cisplatin enter the HCs through MET channel or CTR1. The iron-AG complexes cause mtDNA mutations and affect the protein synthesis. The decrease of ATP synthesis, as well as the translocation of proapoptotic Bcl-2 members (Bax and Bid) will increase the permeability of mitochondrial transmembrane. Thus, leading to the leakage of cyt-c and ROS. The cyt-c will lead to the caspase activation and apoptosis. ROS can cause cell death or amplify insults targeting mitochondria. The iron-AG complexes can catalyze free radical reactions and lead to ROS generation. ROS can also generate via the NOX3 pathway. When JNK was activated by ROS, it will activate some key modulators of apoptosis (c-Jun, c-FOS, ELK-1, and Bcl-2). ROS can also activate STAT1, which will promote proapoptotic actions of cisplatin. AG: aminoglycoside; MET: mechanoelectrical transducer; CTR1: Copper Transporter 1; OCT: organic cation transporter; TRP: transient receptor potential; NOX3: NADPH-oxidase 3; ROS: reactive oxygen species; cyt-c: cytochrome c; STAT1: transcription factor; JNK: c-jun NH2-terminal kinase.