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Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis

  • Authors:
    • Yongqin Li
    • Xueyan Zhao
    • Yujuan Hu
    • Haiying Sun
    • Zuhong He
    • Jie Yuan
    • Hua Cai
    • Yu Sun
    • Xiang Huang
    • Wen Kong
    • Weijia Kong
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3371-3385
    |
    Published online on: October 1, 2018
       https://doi.org/10.3892/ijmm.2018.3907
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Abstract

Central presbycusis is the most common sensory disorder in the elderly population, however, the underlying molecular mechanism remains unclear. NF‑E2‑related factor 2 (Nrf2) is a key transcription factor in the cellular response to oxidative stress, however, the role of Nrf2 in central presbycusis remains to be elucidated. The aim of the present study was to investigate the pathogenesis of central presbycusis using a mimetic aging model induced by D‑galactose (D‑gal) in vivo and in vitro. The degeneration of the cell was determined with transmission electron microscopy, terminal deoxynucleotidyl transferase‑mediated deoxyuridine 5'‑triphosphate nick‑end labeling staining, and senescence‑associated β‑galactosidase staining. The expression of protein was detected by western blotting and immunofluorescence. The quantification of the mitochondrial DNA (mtDNA) 4,834‑base pair (bp) deletion and mRNA was detected by TaqMan quantitative polymerase chain reaction (qPCR) and reverse transcription‑qPCR respectively. Cell apoptosis and intracellular ROS in vitro were determined with flow cytometry. The levels of nuclear Nrf2, and the mRNA levels of Nrf2‑regulated antioxidant genes, were downregulated in the auditory cortex of aging rats, which was accompanied by an increase in 8‑hydroxy‑2'‑deoxyguanosine formation, an accumulation of mtDNA 4,834‑bp deletion, and neuron degeneration. In addition, oltipraz, a typical Nrf2 activator, was found to protect cells against D‑gal‑induced mtDNA damage and mitochondrial dysfunction by activating Nrf2 target genes in vitro. It was also observed that activating Nrf2 with oltipraz inhibited cell apoptosis and delayed senescence. Taken together, the data of the present study suggested that the age‑associated decline in Nrf2 signaling activity and the associated mtDNA damage in the auditory cortex may be implicated in the degeneration of the auditory cortex. Therefore, the restoration of Nrf2 signaling activity may represent a potential therapeutic strategy for central presbycusis.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Zhao X, Hu Y, Sun H, He Z, Yuan J, Cai H, Sun Y, Huang X, Kong W, Kong W, et al: Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis. Int J Mol Med 42: 3371-3385, 2018.
APA
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J. ... Kong, W. (2018). Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis. International Journal of Molecular Medicine, 42, 3371-3385. https://doi.org/10.3892/ijmm.2018.3907
MLA
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J., Cai, H., Sun, Y., Huang, X., Kong, W., Kong, W."Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis". International Journal of Molecular Medicine 42.6 (2018): 3371-3385.
Chicago
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J., Cai, H., Sun, Y., Huang, X., Kong, W., Kong, W."Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis". International Journal of Molecular Medicine 42, no. 6 (2018): 3371-3385. https://doi.org/10.3892/ijmm.2018.3907
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Zhao X, Hu Y, Sun H, He Z, Yuan J, Cai H, Sun Y, Huang X, Kong W, Kong W, et al: Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis. Int J Mol Med 42: 3371-3385, 2018.
APA
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J. ... Kong, W. (2018). Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis. International Journal of Molecular Medicine, 42, 3371-3385. https://doi.org/10.3892/ijmm.2018.3907
MLA
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J., Cai, H., Sun, Y., Huang, X., Kong, W., Kong, W."Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis". International Journal of Molecular Medicine 42.6 (2018): 3371-3385.
Chicago
Li, Y., Zhao, X., Hu, Y., Sun, H., He, Z., Yuan, J., Cai, H., Sun, Y., Huang, X., Kong, W., Kong, W."Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis". International Journal of Molecular Medicine 42, no. 6 (2018): 3371-3385. https://doi.org/10.3892/ijmm.2018.3907
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