Zhang Jianhui, Sun Hong, Salvi Richard, Ding Dalian
Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, China; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA.
Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, China; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA; Department of Audiology and Speech-Language Pathology, Asia University, Taichung, Taiwan, ROC.
Hear Res. 2018 Jul;364:129-141. doi: 10.1016/j.heares.2018.03.014. Epub 2018 Mar 13.
Paraquat (PQ), one of the most widely used herbicides, is extremely dangerous because it generates the highly toxic superoxide radical. When paraquat was applied to cochlear organotypic cultures, it not only damaged the outer hair cells (OHCs) and inner hair cells (IHCs), but also caused dislocation of the hair cell rows. We hypothesized that the dislocation arose from damage to the support cells (SCs) that anchors hair cells within the epithelium. To test this hypothesis, rat postnatal cochlear cultures were treated with PQ. Shortly after PQ treatment, the rows of OHCs separated from one another and migrated radially away from IHCs suggesting loss of cell-cell adhesion that hold the hair cells in proper alignment. Hair cells dislocation was associated with extensive loss of SCs in the organ of Corti, loss of tympanic border cells (TBCs) beneath the basilar membrane, the early appearance of superoxide staining and caspase-8 labeling in SCs below the OHCs and disintegration of E-cadherin and β-catenin in the organ of Corti. Damage to the TBCs and SCs occurred prior to loss of OHC or IHC loss suggesting a form of detachment-induced apoptosis referred to as anoikis.
百草枯（PQ）是使用最广泛的除草剂之一，极具危险性，因为它会产生剧毒的超氧自由基。当将百草枯应用于耳蜗器官型培养物时，它不仅会损伤外毛细胞（OHC）和内毛细胞（IHC），还会导致毛细胞排错位。我们推测这种错位是由于在上皮内锚定毛细胞的支持细胞（SC）受损所致。为了验证这一假设，对大鼠出生后的耳蜗培养物进行了百草枯处理。在百草枯处理后不久，OHC排彼此分离并从IHC径向迁移开，这表明维持毛细胞正确排列的细胞间黏附丧失。毛细胞错位与柯蒂氏器中SC的大量丧失、基底膜下方鼓室边界细胞（TBC）的丧失、OHC下方SC中超氧染色和半胱天冬酶-8标记的早期出现以及柯蒂氏器中E-钙黏蛋白和β-连环蛋白的解体有关。TBC和SC的损伤发生在OHC或IHC丧失之前，提示一种称为失巢凋亡的脱离诱导凋亡形式。
