2. Academic Validation
  3. ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression

ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression

  • Arch Biochem Biophys. 2020 Jul 30;688:108402. doi: 10.1016/j.abb.2020.108402.
Ang Xu 1,  Wenjing Shang 2,  Yan Wang 2,  Xiumei Sun 1,  Bingxin Zhou 2,  Yi Xie 2,  Xiaowen Xu 1,  Tingyan Liu 3,  Fengchan Han 4
Affiliations

Affiliations

  • 1 Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China; Department of Otolaryngology, Yantai Affiliated Hospital of Binzhou Medical University, 717 Jinbu Road of Muping District, Yantai, 264100, Shandong, PR China.
  • 2 Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China; Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China.
  • 3 Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China; Department of Otolaryngology, Yantai Affiliated Hospital of Binzhou Medical University, 717 Jinbu Road of Muping District, Yantai, 264100, Shandong, PR China. Electronic address: lty631230@163.com.
  • 4 Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China; Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China. Electronic address: hanfc2023@bzmc.edu.cn.
PMID: 32418909 DOI: 10.1016/j.abb.2020.108402
Abstract

A/J mouse is a model of age-related hearing loss (AHL). Mutation in the citrate synthase (Cs) gene of the mouse plays an important role in the hearing loss and degeneration of cochlear cells. To investigate the pathogenesis of cochlear cell damage in A/J mice resulted from Cs mutation, we downregulated the expression level of CS in HEI-OC1, a cell line of mouse cochlea, by shRNA. The results showed that low CS expression led to low ability of cell proliferation. Further study revealed an increase level of Reactive Oxygen Species (ROS), activation of ATF6 mediated endoplasmic reticulum stress (ERS) and high expression levels of caspase12 and Bax in the cells. Moreover, the AEBSF, an ATF6 inhibitor, could reduce the expression levels of caspase-12 and Bax by inhibiting the hydrolysis of ATF6 in the cells. Finally, antioxidant alpha-lipoic acid (ALA) reduced the ROS levels and the apoptotic signals in the cell model with low CS expression. We therefore conclude that the ERS mediated Apoptosis, which is triggered by ROS, may be involved in the cell degeneration in the cochleae of A/J mice.

Keywords

Age-related hearing loss; Apoptosis; Citrate synthase; Endoplasmic reticulum stress; ROS; α-lipoic acid.

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