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Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of d-galactose-induced aging rats

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Abstract

Aging has been associated with mitochondrial DNA (mtDNA) common deletion (CD). Age changes in the central auditory system are well known to affect speech perception. Base excision repair (BER) is the major type of DNA repair in mitochondria. The current study was designed to investigate potential causative mechanisms of central presbycusis by using a rat mimetic aging model induced by subcutaneous administration of d-galactose (d-gal). Quantitative real-time PCR and Western blotting analyses were performed to identify the mtDNA 4834 bp deletion and selected mitochondrial DNA repair enzymes, DNA polymerase γ (pol γ) and 8-oxoguanine DNA glycosylase (OGG1). Cell apoptosis in the auditory cortex was detected using terminal deoxynucleotidyltransferase mediated UTP nick-end labeling (TUNEL). Our data showed that mtDNA 4834 bp deletion and TUNEL-positive cells were significantly increased and the expression of pol γ and OGG1 were remarkably down-regulated in the auditory cortex in d-gal-treated rats compared to control rats. During aging, increased mtDNA damage likely results from decreased DNA repair capacity in the auditory cortex. DNA repair enzymes such as pol γ and OGG1 may provide novel pharmacological targets to promote DNA repair and rescue the central auditory system in patients with degenerative diseases.

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Abbreviations

BER:

Mitochondrial base excision repair

AHL:

Age-related hearing loss

d-gal:

d-Galactose

mtDNA:

Mitochondrial DNA

CD:

Common deletion

AC:

Auditory cortex

OGG1:

8-Oxoguanine DNA glycosylase

DNA pol γ:

DNA polymerase γ

TUNEL:

Terminal deoxynucleotidyltransferase-mediated UTP nick-end labeling

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Acknowledgment

This work was supported by grant from a National Nature Science Foundation of China (No. 30730094).

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Authors and Affiliations

  1. Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China

    Bei Chen, Yi Zhong, Wei Peng, Yu Sun, Yu-juan Hu, Yang Yang & Wei-jia Kong

  2. Department of Otolaryngology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Avenue, Zhengzhou, 450002, China

    Bei Chen

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  1. Bei Chen
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  3. Wei Peng
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Correspondence to Wei-jia Kong.

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B. Chen and Y. Zhong contributed equally to this work.

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Chen, B., Zhong, Y., Peng, W. et al. Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of d-galactose-induced aging rats. Mol Biol Rep 38, 3635–3642 (2011). https://doi.org/10.1007/s11033-010-0476-5

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  • DOI: https://doi.org/10.1007/s11033-010-0476-5

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