title: PARP-1-modulated AIF translocation is involved in streptomycin-induced cochlear hair cell death.
abstract: Conclusion SM-induced dose- and location-dependent cochlear hair cell death in vitro. AIF might be translocated from mitochondria to nucleus and cytoplasm within SM-treated hair cells. The translocation of AIF might be modulated by PARP-1. Objective Streptomycin (SM), one of the widely used aminoglycoside nowadays, is still causing significant permanent sensorineural hearing loss owing to sensory hair cell death. This study was designed to investigate the role of apoptosis-inducing factor (AIF), an important mitochondrial cell death regulator, in SM ototoxicity within neonatal rat cochleae and HEI-OC1 cells. Methods The viability of HEI-OC1 cells was quantified by MTT assay. AIF, PARP-1, and myosin VIIa distributions were achieved by immunofluorescence. mRNA and protein expression of AIF and PARP-1 were examined by q-PCR and Western-blot. Results The hair cell loss was concomitant with the SM concentration variation, and aggravated from apical to basal turn. AIF was detected in nuclear region and AIF mRNA was up-regulated after SM incubation. Besides, AIF protein expression in mitochondria was decreased, whereas in cytosol it was increased. PARP-1 mRNA and protein were also up-regulated. 3-AB could attenuate the cell death and reverse the changes of AIF distribution by blocking PARP-1.
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;|b Shandong Provincial Key Laboratory of Otology , Jinan , PR China ;
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Song
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: b Shandong Provincial Key Laboratory of Otology , Jinan , PR China ;|c Institute of Eye and ENT, Shandong Provincial Hospital Afﬁliated to Shandong University , Jinan , PR China ;
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: b Shandong Provincial Key Laboratory of Otology , Jinan , PR China ;|c Institute of Eye and ENT, Shandong Provincial Hospital Afﬁliated to Shandong University , Jinan , PR China ;
authors.forename: Wenwen
authors.initials: W
authors.lastname: Liu
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Han
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.affiliation: b Shandong Provincial Key Laboratory of Otology , Jinan , PR China ;|c Institute of Eye and ENT, Shandong Provincial Hospital Afﬁliated to Shandong University , Jinan , PR China ;
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: d Department of Otolaryngology-Head and Neck Surgery , Case Western Reserve University , Cleveland , OH , USA.
authors.forename: Qingyin
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
authors.forename: Daogong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery , Shangdong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;|b Shandong Provincial Key Laboratory of Otology , Jinan , PR China ;|c Institute of Eye and ENT, Shandong Provincial Hospital Afﬁliated to Shandong University , Jinan , PR China ;
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000378:metabolism; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D051033:Apoptosis Inducing Factor; C499321:Parp1 protein, mouse; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: HEI-OC1 cell; Streptomycin ototoxicity; cochleae organotypic culture; programmed cell death