TIGAR protects cochlear hair cells against teicoplanin-induced damage

Abstract

Abstract Teicoplanin, a glycopeptide antibiotic, is used for the treatment of severe staphylococcal infections. Teicoplanin is reported to have an ototoxic potential but its toxic effects on cochlea hair cells (HCs) remains unclear. TP53-induced glycolysis and apoptosis regulator (TIGAR) plays a key role to promote cell survival, our previous study shown that TIGAR protected inner ear spiral ganglion neuron against cisplatin injury. However, the role of TIGAR in mammalian HCs damage has not been explored yet. In this study, firstly, we found that teicoplanin induced significant cell loss of both HEI-OC1 cells and cochlea HCs in a dose-dependent manner in vitro. Next, we discovered that the expression of TIGAR was significantly decreased after teicoplanin treatment in HCs and HEI-OC1 cells. To explore the role of TIGAR in inner ear after teicoplanin damage, the expression of TIGAR was upregulated via recombinant adenovirus or knocked down by shRNA in HEI-OC1 cells, respectively. We found that the overexpression of TIGAR increased cell viability, decreased apoptosis and reduced intracellular reactive oxygen species (ROS) level after teicoplanin injury, whereas downregulation of TIGAR by shRNA decreased cell viability, exacerbated apoptosis and elevated ROS level. Finally, antioxidant treatment with N-acetyl-L-cysteine lowered ROS level, rescued cell loss as well as restored p38/phosphorylation-p38 expression levels induced by TIGAR deficiency in HEI-OC1 cells after teicoplanin injury. This study provides evidences that TIGAR might be a new potential target for prevention from the teicoplanin-induced ototoxicity.