Detection of apoptosis by RT-PCR array in mefloquine-induced cochlear damage

作     者：DING Da-lian Someya Shinichi JIANG Hai-yan QI Wei-dong YU Dong-zhen 

作者机构：Center for Hearing and Deafness State University of New York at Buffalo Departments of Aging and Geriatric Research Division of Biology of Aging University of Florida Department of Otolaryngology Head and Neck Surgery Huashan Hospital Affiliated Fudan University Department of Otolaryngology Head and Neck Surgery Six People＇s Hospital of Shanghai Jiao Tong University Graduate School of Agricultural and Life Sciences University of Tokyo Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University 

出 版 物：《Journal of Otology》 (中华耳科学杂志（英文版）)

年 卷 期：2011年第6卷第1期

页      面：1-9页

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 09[农学] 0902[农学-园艺学] 090201[农学-果树学] 

主　　题：mefloquine ototoxicity apoptosis cochlea spiral ganglion neurons hair cells gene expression 

摘      要：Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays （96-well, 84 apoptosis related genes） to assess changes of gene expression in the cochlear basilar membrane （hair cells-supporting cells） and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.