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Acta Oto-Laryngologica Volume 136, 2016 - Issue 6
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Original Article

PARP-1-modulated AIF translocation is involved in streptomycin-induced cochlear hair cell death

Yongdong SongDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; ;Shandong Provincial Key Laboratory of Otology, Jinan, PR China;
,
Zhaomin FanDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Xiaohui BaiShandong Provincial Key Laboratory of Otology, Jinan, PR China; ;Institute of Eye and ENT, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Wenwen LiuShandong Provincial Key Laboratory of Otology, Jinan, PR China; ;Institute of Eye and ENT, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Yuechen HanDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Lei XuDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Mingming WangDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Jianfeng LiShandong Provincial Key Laboratory of Otology, Jinan, PR China; ;Institute of Eye and ENT, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China;
,
Qingyin ZhengDepartment of Otolaryngology-Head and Neck Surgery, Case Western Reserve University, Cleveland, OH, USA
,
Daogong ZhangDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Correspondence[email protected]
&
Haibo WangDepartment of Otolaryngology-Head and Neck Surgery, Shangdong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; ;Shandong Provincial Key Laboratory of Otology, Jinan, PR China; ;Institute of Eye and ENT, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Correspondence[email protected]
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Pages 545-550 | Received 15 Nov 2015, Accepted 11 Jan 2016, Published online: 10 Mar 2016
 
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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.

Acknowledgments

We thank Dr Federico Kalinec, ULCA for providing the HEI-OC1 cell line. This study was supported by the Natural Science Foundation of China (81200744); The research special fund for public welfare industry of health (201202001); Natural Science Foundation of China (81170907); Science and Technology Development Program of Shandong province (2011GGH21839); Youth Fund Project of Shandong provincial Medical technology development plan (2011WSB02002); National Science & Technology Pillar Program during the 12th Five-year Plan Period (2012BAI12B02).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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