Epithelial Cells Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, ShaTin, Hong Kong.
PLoS One. 2011 Feb 25;6(2):e17322. doi: 10.1371/journal.pone.0017322.
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 stage.
听力损失或耳毒性是与抗生素使用相关的主要副作用之一，特别是氨基糖苷类（AGs），它们是全球最常用的抗生素。然而，抗生素诱导的耳毒性涉及的分子和细胞事件仍不清楚。在本研究中，我们测试了一种可能性，即 prestin，一种在外毛细胞（OHCs）的基底外侧膜中特异性表达的运动蛋白，具有负责声音放大的电动力，可能参与了 AG 诱导的 OHCs 细胞凋亡过程。我们从小鼠模型和培养细胞系获得的结果表明 prestin 具有一个以前未被发现的作用，即在介导抗生素诱导的细胞凋亡中发挥作用，其作用与阴离子转运能力有关。在抗生素处理的小鼠中，OHCs 出现凋亡和听力损失之前，观察到 prestin mRNA 的下调，这很有趣，它可能在 AGs 诱导的听力损失的早期阶段作为一种保护机制。
