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AdipoRon reduces cisplatin-induced ototoxicity in hair cells:possible relation to the regulation of mitochondrial biogenesis.
Nong, Huiming; Song, Xinlei; Li, Yanan; Xu, Yue; Wang, Fan; Wang, Yajie; Zhang, Junhong; Chen, Chengfang; Li, Jianfeng.
Afiliação
  • Nong H; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • Song X; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.
  • Li Y; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • Xu Y; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.
  • Wang F; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.
  • Wang Y; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • Zhang J; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.
  • Chen C; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021,
  • Li J; Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; Central Lab, Shandong Provincial Hospital Affiliated to Shandong First University, Jinan, Shandong 250021, China; Shandong Provincial Key L
Neurosci Lett ; 819: 137577, 2024 Jan 10.
Article em En | MEDLINE | ID: mdl-38072030
AdipoRon (AR) can exert antidiabetic and anti-inflammatory effects by maintaining mitochondrial structure and function. The present study was designed to explore whether AR protects the auditory cells from cisplatin-induced damage and, if so, to probe the possible mechanisms underlying its action on this type of cells. Cell viability and apoptosis in House Ear Institute-Organization of Corti 1 (HEI-OC1 cells) and mouse cochlea hair cells (HCs) were detected by CCK8 and immunofluorescence. The expressions of apoptosis-related proteins (cleaved caspase-3 and Bcl-2), adiponectin receptor 1 (AdipoR 1) and the key factors relevant to mitochondrial biogenesis(SIRT1 and TFAM)were determined by Western blot and immunofluorescence. Changes in apoptotic rate and expression of SIRT1 and TFAM after silencing of AdipoR 1 (AdipoR 1-siRNA) in HEI-OC1 cells were measured by flow cytometry and Western blot. The levels of reactive oxygen species (ROS) were evaluated by MitoSox red staining. We found that 30 µM cisplatin exposure induced severe cellular damage, which resulted from activation of the mitochondrial apoptotic pathway. Cisplatin decreased the expression of AdipoR 1, SIRT1, and TFAM proteins, leading to impaired mitochondrial biogenesis and increased mitochondrial ROS production. 10 µM AR pre-treatment enhanced mitochondrial biogenesis, decreased mitochondrial ROS levels, alleviated imbalances in the mitochondrial apoptotic pathway, thus reducing cisplatin-induced apoptosis. Taken together, this work reveals that AR exerts anti-apoptotic effects, possibly via regulating mitochondrial biogenesis and function. Interestingly, AR might possess the promising potential to be a novel drug for the prevention and/ or treatment of cisplatin-induced ototoxicity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ototoxicidade / Antineoplásicos Limite: Animals Idioma: En Revista: Neurosci Lett Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ototoxicidade / Antineoplásicos Limite: Animals Idioma: En Revista: Neurosci Lett Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China