The role of peroxiredoxin I in cisplatin-induced ototoxicity.
The role of peroxiredoxin I in cisplatin-induced ototoxicity.
复制标题
过氧化还原蛋白 I 在顺铂诱导的耳毒性中的作用。
DOI：
10.1016/j.anl.2016.06.001
复制
发表时间：
2016
影响因子：
1.7
通讯作者：
Hara A.
中科院分区：
文献类型：
--
作者：
Le Q;Tabuchi K;Warabi E;Hara A.
目的过氧化还原蛋白（Prx）是一个新的抗氧化蛋白家族。 Prx I 在各种组织中普遍表达，对于保护组织免受活性氧 (ROS) 增加的影响非常重要。本研究旨在检测小鼠耳蜗中 Prx 亚型的表达，并表明 Prx I 可能参与保护耳蜗免受顺铂耳毒性。方法使用出生后第 3 至 5 天的野生型小鼠和 Prx I 缺陷小鼠。通过实时 PCR 测定评估耳蜗中的 Prx 表达。通过免疫荧光染色检查 Prx I 蛋白表达。将耳蜗外植体暴露于 2、5 和 10 μM 顺铂 48 小时，并比较野生型和 Prx I 缺陷型小鼠的耳蜗毛细胞损失。此外，顺铂孵育后观察耳蜗侧壁的组织学特征。结果所有Prx亚型的mRNA在小鼠耳蜗中均有表达。 Prx I 是丰富的亚型之一，暴露于 5 μM 顺铂 48 小时后表达上调。免疫荧光染色显示 Prx I 在耳蜗中普遍表达。野生型小鼠和 Prx I 缺陷型小鼠之间未发现顺铂诱导的耳蜗毛细胞损失存在差异。然而，Prx I缺陷小鼠的螺旋韧带纤维细胞对20μM或更低的顺铂显着敏感。结论在顺铂耳毒性中，Prx I对于至少保护耳蜗侧壁的螺旋韧带纤维细胞具有重要意义。
ObjectivePeroxiredoxin (Prx) is a new family of antioxidative proteins. Prx I is ubiquitously expressed in various tissues and is important in the defense of tissues from increases in reactive oxygen species (ROS). The present study was designed to examine the expression of Prx subtypes in the mouse cochlea and to show the possible involvement of Prx I in protecting the cochlea against cisplatin ototoxicity.MethodsPostnatal-day-3-to-5 wildtype mice and Prx I-deficient mice were used. Prx expression in the cochlea was assessed by real-time PCR assay. Prx I protein expression was examined by immunofluorescence staining. Cochlear explants were exposed to 2, 5, and 10-μM cisplatin for 48 h, and the cochlear hair cell losses of the wildtype and Prx I-deficient mice were compared. In addition, the histologic features of the cochlear lateral wall were examined after cisplatin incubation.ResultsmRNAs of all Prx subtypes were expressed in the mouse cochlea. Prx I was one of the abundant subtypes and was upregulated after 48-h exposure to 5-μM cisplatin. Immunofluorescence staining showed the ubiquitous expression of Prx I in the cochlea. No difference in cochlear hair cell loss induced by cisplatin was found between the wildtype mice and the Prx I-deficient mice. However, spiral ligament fibrocytes of Prx I-deficient mice were significantly sensitive to cisplatin at 20-μM or lower.ConclusionPrx I is important for protection of at least the spiral ligament fibrocytes of the cochlear lateral wall in cisplatin ototoxicity.