Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Hear Res. 2010 Mar;261(1-2):67-74. doi: 10.1016/j.heares.2010.01.004. Epub 2010 Jan 13.
Gentamicin induces outer hair cell death through the apoptotic pathway. It has been reported that this death pathway of outer hair cells is mediated by specific apoptotic enzymes including c-jun N-terminal kinase (JNK) and caspases. 17beta-Estradiol (E2), the most potent estrogen, is known to function as an antiapoptotic agent to prevent the death of various cell types. The purpose of the present study was to examine the effects of E2 on gentamicin-induced apoptotic cell death in outer hair cells. The basal turn organ of Corti explants from p3 or p4 rats were maintained in a tissue culture and exposed to 100muM gentamicin for 48h. The effects of E2 on gentamicin-induced outer hair cell loss, JNK activation, and staining for terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling (TUNEL) were examined. E2 significantly decreased gentamicin-induced outer hair cell loss in a dose-dependent manner. JNK activation and TUNEL staining were observed in organ of Corti explants exposed to gentamicin, and staining levels were significantly decreased by E2 treatment. The results indicate that, through the inhibition of JNK and subsequent apoptotic reactions, E2 decreases outer hair cell loss induced by gentamicin ototoxicity.
庆大霉素通过凋亡途径诱导外毛细胞死亡。据报道，外毛细胞的这种死亡途径是由包括 c-jun N 末端激酶 (JNK) 和半胱天冬酶在内的特定凋亡酶介导的。17β-雌二醇 (E2) 是最有效的雌激素，已知其具有抗凋亡作用，可防止各种细胞类型的死亡。本研究的目的是研究 E2 对庆大霉素诱导的外毛细胞凋亡的影响。从 p3 或 p4 大鼠的耳蜗底回组织中分离出的器官培养物，并在组织培养中维持 48 小时，然后暴露于 100μM 的庆大霉素中。检测 E2 对庆大霉素诱导的外毛细胞丢失、JNK 激活和末端脱氧核苷酸转移酶介导的生物素化 UTP 缺口末端标记 (TUNEL) 染色的影响。E2 以剂量依赖性方式显著降低庆大霉素诱导的外毛细胞丢失。在暴露于庆大霉素的耳蜗器官培养物中观察到 JNK 激活和 TUNEL 染色，并且 E2 处理可显著降低染色水平。结果表明，E2 通过抑制 JNK 及其随后的凋亡反应，减少庆大霉素耳毒性诱导的外毛细胞丢失。
