Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides
Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides
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DOI：
10.1080/03655230310016799
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发表时间：
2004-03-01
影响因子：
1.4
通讯作者：
Ito, J
中科院分区：
文献类型：
--
作者：
Lee, JE;Nakagawa, T;Ito, J
以前关于哺乳动物前庭毛细胞再生的研究表明，受损的毛细胞具有自我修复的潜力。因此，将受损的毛细胞从细胞死亡中拯救出来可能会增加受影响的前庭上皮中再生的毛细胞。细胞凋亡在氨基糖苷类药物治疗后前庭毛细胞退化中的作用已被阐明。为了寻找一种保护前庭毛细胞免受氨基糖苷类毒性作用的方法，我们检测了氨基糖苷类毒性引起的前庭毛细胞的凋亡信号通路。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法和透射电子显微镜观察了局部应用新霉素对小鼠壶腹脊毛细胞的诱导凋亡作用。采用免疫组织化学方法检测毛细胞凋亡相关蛋白的表达，确定毛细胞凋亡的信号通路。原位末端标记法和透射电子显微镜显示毛细胞发生凋亡。在凋亡的毛细胞中，caspase-3和-9被激活，细胞色素c重新分布，而caspase-8和凋亡诱导因子未见表达。总而言之。提示线粒体介导的细胞凋亡途径可能在氨基糖苷类毒性所致的前庭毛细胞凋亡中起一定作用。因此，线粒体膜的稳定可能会使前庭毛细胞免于凋亡，导致受影响的前庭上皮中自我修复的毛细胞增加。
Previous studies on regeneration of mammalian vestibular hair cells have indicated the potential for self-repair of damaged hair cells. The rescue of damaged hair cells from cell death may therefore increase regenerated hair cells in affected vestibular epithelia. The role of apoptosis in the degradation of vestibular hair cells following aminoglycoside treatment has been elucidated. To seek a method of protecting vestibular hair cells from aminoglycoside toxicity, we examined the apoptosis signaling pathway of vestibular hair cells due to aminoglycoside toxicity. Induction of apoptosis in hair cells of mouse ampullar cristae damaged by local application of neomycin was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method and transmission electron microscopy (TEM). Immunohistochemistry for apoptosis-related proteins was employed to determine the signaling pathway of apoptosis of hair cells. The occurrence of apoptosis in hair cells was demonstrated by TUNEL staining and TEM. In apoptotic hair cells, activation of caspase-3 and -9, and redistribution of cytochrome c was identified, while there was no expression of activated caspase-8 or apoptosis-inducing factor. In conclusion. these findings indicate that the mitochondria-mediated pathway of apoptosis may play a role in inducing the apoptosis of vestibular hair cells due to aminoglycoside toxicity. Stabilization of the mitochondrial membrane may therefore rescue vestibular hair cells from apoptosis, leading to an increase in self-repaired hair cells in affected vestibular epithelia.