2. Academic Validation
  3. DJ-1 Protects auditory cells from cisplatin-induced ototoxicity via regulating apoptosis and autophagy

DJ-1 Protects auditory cells from cisplatin-induced ototoxicity via regulating apoptosis and autophagy

  • Toxicol Lett. 2023 Mar 24;379:56-66. doi: 10.1016/j.toxlet.2023.03.010.
Yajie Wang 1,  Hao Zhao 2,  Fan Wang 1,  Huiming Nong 1,  Yanan Li 1,  Yue Xu 1,  Mingqiang He 3,  Jianfeng Li 4
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • 2 Department of Otolaryngology, Head and Neck Surgery, People's Hospital, Peking University, Beijing, China.
  • 3 Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address: [email protected].
  • 4 Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Institute of Eye and ENT, Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China; Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China. Electronic address: [email protected].
PMID: 36965608 DOI: 10.1016/j.toxlet.2023.03.010
Abstract

Aims: DJ-1, a multifunctional protein encoded by the Park7 gene, is tightly related to mitochondrial dysfunction, oxidative stress, protein aggregation, and Autophagy regulation. The current study was designed to investigate whether DJ-1 is expressed in auditory cells and, if so, to explore the possible correlation between DJ-1 and cisplatin-induced ototoxicity in this type of cells.

Methods: The location and dynamic expression of DJ-1 in mouse cochlea hair cells (HCs) and House Ear Institute-Organ of Corti 1 (HEI-OC1 cells) were detected by immunofluorescence, Real-Time PCR, and western blot. The Apoptosis of auditory cells was assessed by TUNEL staining and flow cytometry. The levels of ROS were evaluated by MitoSox red staining. The expression of protein cleaved caspase-9, cleaved Caspase-3, and LC3B was examined by immunofluorescence and western blot. The expressions of certain key factors relevant to Apoptosis (Bcl-2 and Bax) and Autophagy (Beclin1, p-JNK, and p-c-Jun) were determined by western blot. The dynamic alterations of those factors in response to DJ-1 knockdown in HEI-OC1 cells (DJ-1-KD) were measured by western blot and MitoSox red staining.

Results: The expression of DJ-1 was clearly shown in both HCs and HEI-OC1 cells and cisplatin led to the reduction of DJ-1 expression in a concentration and time-dependent manner. Meanwhile, cisplatin-induced apoptotic process was implemented by promoting Reactive Oxygen Species (ROS) production and activating the mitochondrial pathway. Furthermore, DJ-1 explicitly participated in cisplatin-trigged cell damage by regulating Autophagy.

Conclusions: Findings from this work clearly reveal, for the first time, that DJ-1 is expressed in the cochlea. Of particular importance, DJ-1 exerts its protective action against cisplatin-elicited injury on auditory cells via regulating Apoptosis and Autophagy, which provides a new strategy for the prevention of cisplatin-induced ototoxicity.

Keywords

Apoptosis; Autophagy; Cisplatin; DJ-1; Reactive oxygen species.

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