Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity
Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity
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DOI：
10.1016/s0378-5955(01)00417-8
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发表时间：
2002-02-01
期刊：
影响因子：
2.8
通讯作者：
Salvi, RJ
中科院分区：
文献类型：
--
作者：
Ding, DL;Stracher, A;Salvi, RJ
钙蛋白酶是一种钙激活的蛋白酶家族，它能分解蛋白质、激酶、磷酸酶和转录因子，能促进细胞死亡。亮抑酶肽是一种钙蛋白酶抑制剂，能保护耳蜗和前庭毛细胞免受庆大霉素耳毒性的影响。为了检验这一假设，将来自耳蜗、椭圆囊黄斑和半规管嵴（P1-P3）的小鼠器官型培养物单独用不同剂量的GM（0.1-3 mM）处理或在亮抑酶肽（0.1 -3 mM）存在下处理。外毛细胞（OHCs）和内毛细胞（IHCs）的百分比随着GM剂量的增加而降低，在0.1和3 mM之间。加入1 mM亮抑酶肽显着降低GM诱导的对IHCs和OHCs的损伤;这种保护作用是剂量依赖性的。在0.1和3 mM之间，GM还以剂量依赖性方式显著降低嵴和椭圆囊中的毛细胞密度。对于0.1和3 mM之间的GM浓度，添加1 mm亮抑酶肽显著降低嵴和椭圆囊中的毛细胞损失。导致耳蜗和前庭毛细胞死亡的活化蛋白酶。(C)2002 Elsevier Science B. V.保留所有权利。
Calpains, a family of calcium-activated proteases that breakdown proteins, kinases, phosphatases and transcription factors, can promote cell death, Since leupeptin, a calpain inhibitor, protected against hair cell loss from acoustic overstimulation, we hypothesized that it might protect cochlear and vestibular hair cells against gentamicin (GM) ototoxicity. To test this hypothesis, mouse organotypic cultures from the cochlea, maculae of the utricle and the crista of the semicircular canal (P1-P3) were treated with different doses of GM (0.1-3 mM) alone or in the presence of leupeptin (0.1-3 mM). The percentage of outer hair cells (OHCs) and inner hair cells (IHCs) decreased with increasing doses of GM between 0.1 and 3 mM. The addition of I mM of leupeptin significantly reduced GM-induced damage to IHCs and OHCs; this protective effect was dose-dependent. GM also significantly reduced hair cell density in the crista and utricle in a dose-dependent manner between 0.1 and 3 mM. The addition of I mm of leupeptin significantly reduced hair cell loss in the crista and utricle for GM concentrations between 0.1 and 3 mM. These results suggest that one of the early steps in GM ototoxicity may involve calcium-activated proteases that lead to the demise of cochlear and vestibular hair cells. (C) 2002 Elsevier Science B.V. All rights reserved.