Mechanisms of apoptosis induced by cisplatin in marginal cells in mouse stria vascularis
Mechanisms of apoptosis induced by cisplatin in marginal cells in mouse stria vascularis
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DOI：
10.1159/000079329
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Ito, J
中科院分区：
文献类型：
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作者：
Lee, JE;Nakagawa, T;Ito, J
血管纹(SV)变性是顺铂(CDDP)致听力损害的主要原因之一。用小鼠实验模型研究了CDDP引起的SV细胞凋亡的途径。分别于局部应用CDDP后第3、7、14天采集成年C57BL/6小鼠的颞骨。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法和细胞凋亡相关蛋白或活性自由基类的免疫组织化学方法进行分析。CDDP局部应用后3d可引起边缘细胞凋亡。免疫组织化学分析显示caspase-3和-9被激活，而不是-8被激活，细胞色素c在受影响的边缘细胞中重新分布，这表明边缘细胞中存在caspase依赖的线粒体介导的凋亡途径。在诱导边缘细胞凋亡的过程中，观察到羟基壬烯醛、硝基酪氨酸和诱导型一氧化氮合酶在视网膜室的暂时表达。CDDP毒性在SV中产生活性自由基，导致线粒体膜通透性，导致边缘细胞凋亡。版权所有(C)2004 S.Karger AG，巴塞尔。
Degeneration of the stria vascularis (SV) is amongst the major causes of cisplatin (CDDP)-induced hearing impairment. The pathways of apoptosis occurring in the SV due to CDDP were examined using a mouse experimental model. Temporal bones of adult C57BL/6 mice were collected on days 3, 7 and 14 after the local application of CDDP. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and immunostaining for apoptosis-related proteins or reactive radical species were employed for analysis. Local application of CDDP caused apoptotic cell death of marginal cells 3 days after CDDP treatment. Immunohistochemical analyses demonstrated activation of caspase-3 and - 9, but not - 8, and redistribution of cytochrome c in affected marginal cells, indicating a caspase-dependent, mitochondrion-mediated apoptotic pathway in marginal cells. Temporary expression of hydroxynonenal, nitrotyrosine and inducible nitric oxide synthase in the SV was observed at the induction of apoptosis in marginal cells. CDDP toxicity generates reactive radical species in the SV, which causes mitochondrial membrane permeabilization leading to apoptosis of marginal cells. Copyright (C) 2004 S. Karger AG, Basel.