Attenuation of ROS Generation by KCNE1 Genes in Cisplatin-treated Auditory Cells

Potassium is essential for the proper functioning of the ears. The inner ear's endolymph differs from all other extracellular fluids (in its positive potential) and in the ionic compositions in the various parts of the endolymphatic space. Ion concentration of the endolymph is 150 mM of potassium, which is comparable to the concentrations in other organs. Cisplatin (cis-diamminedichloroplatinum II: CDDP) is one of the most effective anticancer drugs, widely used against various tumors. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. For ototoxicity, a number of evidences in cytotoxic mechanism of cisplatin, including perturbation of redox status, increase in lipid peroxydation, and formation of DNA adduct, have been suggested. Therefore, in this study, the author investigated the relationship between the potassium ions on cisplatin-induced cytotoxicity in HEI-OC1 cells associated with reactive oxygen species (ROS). KCNE1 gene expression by the concentration of intracellular potassium appeared in the plasma membrane and increased the concentration of intracellular potassium. Cisplatin decreased the viability of HEI-OC1 cells, but the KCNE1 gene increased. Also, the KCNE1 gene significantly suppressed generation of intracellular ROS by cisplatin. Western blot analysis showed that the KCNE1 gene increased phase II detoxification enzymes markers such as superoxide dismutase 1 (SOD1), superoxide dismutase (SOD2), NAD(P)H:quinine oxidoreductases (NQO1), which were associated with the scavenger of ROS. These results suggest that the KCNE1 gene for intracellular potassium concentration ultimately prevents ROS generation from cisplatin and further contributes to protect auditory sensory hair cells from ROS produced by cisplatin.