Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea
Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea
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DOI：
10.1016/s0378-5955(99)00211-7
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发表时间：
2000-03-01
期刊：
影响因子：
2.8
通讯作者：
Takasaka, T
中科院分区：
文献类型：
--
作者：
Alam, SA;Ikeda, K;Takasaka, T
众所周知，顺铂会引起耳蜗毒性。为了确定顺铂诱导耳蜗细胞死亡的潜在机制，我们研究了细胞凋亡的变化和控制细胞凋亡的bcl-2家族蛋白的表达。给沙鼠顺铂4 mg/kg/d，连续5 d。与年龄匹配的对照组相比，顺铂治疗的动物在畸变产物耳声发射和耳蜗电位的反应中表现出明显的恶化，表明外毛细胞和血管纹功能障碍。通过末端脱氧核苷酸转移酶介导的dutp -生物素缺口末端标记方法，在顺铂治疗动物的Corti器官、螺旋神经节和血管纹中发现了DNA片段的存在，而在对照组动物中几乎得到了阴性结果。Hoechst 33342染色显示细胞核缩缩，证实了细胞凋亡的特征。顺铂治疗后，在Corti器官、螺旋神经节和侧壁细胞中分别观察到bax-和bcl-2阳性细胞数量的显著增加和减少。这些发现提示bcl-2家族蛋白在顺铂诱导的凋亡细胞死亡调控中起关键作用。本文讨论了顺铂诱导细胞死亡的潜在机制。(C) 2000 Elsevier Science B.V.版权所有
Cisplatin is well known to cause cochleotoxicity. In order to determine the underlying mechanisms of cisplatin-induced cell death in the cochlea, we investigated the apoptotic changes and the expression of bcl-2 family proteins controlling apoptosis. Mongolian gerbils were administered 4 mg/kg/day cisplatin consecutively for 5 days. The cisplatin-treated animals showed a significant deterioration in the responses of both distortion product otoacoustic emissions and the endocochlear potential as compared with those of the age-matched controls, suggesting outer hair cell and stria vascularis dysfunction. The presence of DNA fragmentation revealed by a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling method was recognized in the organ of Corti, the spiral ganglion, and the stria vascularis in the cisplatin-treated animals whereas almost negative results were obtained in the control animals. The nuclear morphology obtained by Hoechst 33342 staining revealed pyknotic and condensed nuclei, confirming the presence of the characteristic features of apoptosis. A significant increase and reduction in the number of bax- and bcl-2-positive cells, respectively, following cisplatin treatment was observed in the cells of the organ of Corti, the spiral ganglion, and the lateral wall. These findings suggest a critical role for bcl-2 family proteins in the regulation of apoptotic cell death induced by cisplatin. The underlying mechanisms of the cisplatin-induced cell death are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.