title: Role of autophagy in cisplatin-induced ototoxicity.
abstract: OBJECTIVE
  Hearing loss is a major side effect of cisplatin chemotherapy. Although cell death in cisplatin-induced ototoxicity is primarily caused by apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not fully understood. Autophagy is generally known as a pro-survival mechanism that protects cells under starvation or stress conditions. However, recent research has reported that autophagy plays a functional role in cell death also. This study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity in an auditory cell line.
  
  
  METHODS
  Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 48 h, and cell viability was tested using MTT assays. To evaluate whether autophagy serves to cell death after cisplatin exposure, western blotting and immunofluorescence staining for LC3-II were performed. Markers of two autophagy-related pathways, mTOR and class III PI3K, were also investigated.
  
  
  RESULTS
  The formation of the autophagic protein LC3-II in response to 30 μM cisplatin increased with time. The early upregulation of autophagy exerted cytoprotective activity via the class III PI3K pathway. But later increase in autophagy induced cell death by suppressing the mTOR pathway.
  
  
  CONCLUSIONS
  Our results prove that autophagy could induce cell death during cisplatin-induced ototoxicity, and modulating the autophagic pathway might be another strategy against cisplatin-induced ototoxicity.
authors: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea; Division of Natural Medical Science, Chosun University School of Medicine, Gwangju, South Korea.
authors: Cha Kyung
authors: CK
authors: Youn
authors: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
authors: Jun
authors: J
authors: Kim
authors: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
authors: Jun-Hee
authors: JH
authors: Park
authors: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea.
authors: Nam Yong
authors: NY
authors: Do
authors: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, Gwangju, South Korea. Electronic address: chosi@chosun.ac.kr.
authors: Sung Il
authors: SI
authors: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C480860:Map1lc3b protein, mouse; C546843:mTOR protein, mouse
keywords: Autophagy; Cell death; Cisplatin; Hearing loss; Ototoxicity