a protective mechanism against antibiotic-induced ototoxicity role of prestin保护机制对antibiotic-induced prestin的耳毒性作用.pdfVIP

A Protective Mechanism against Antibiotic-Induced Ototoxicity: Role of Prestin 1,2,3 1 1 1 1 1 1 Li Yu , Xiao Hua Jiang , Zhen Zhou , Lai Ling Tsang , Mei Kuen Yu , Yiu Wa Chung , Xiao Hu Zhang , 2 3 1 Ai Mei Wang , Hao Tang *, Hsiao Chang Chan * 1 Epithelial Cells Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, ShaTin, Hong Kong, 2 Department of Physiology, Liao Ning Medical University, Jin Zhou, Liao Ning, China, 3 Department of Physiology, China Medical University, Shen Yang, Liao Ning, China Abstract Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic- induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early st