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Mitochondrial DNA Damage and the Involvement of Antioxidant Defense and Repair System in Hippocampi of Rats with Chronic Seizures

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Abstract

In this study, we demonstrated a decreased level of mitochondrial DNA (mtDNA) with a large number of oxidized bases in hippocampi of rats with epilepsy induced by pilocarpine. In order to verify the underlying mechanism of mtDNA impairment, we detected the response of antioxidant defense system and mitochondrial base excision repair (mtBER) pathway. Superoxide dismutase2 (SOD-2) and glutathione (GSH) were significantly decreased in the experimental group, manifesting a decreased capacity of scavenging free radicals. Mitochondrial base excision repair (mtBER) pathway, which is the main repair pathway for the removal of oxidative base modifications, displayed unbalanced expression in epileptic group. DNA polymeraseγ (polγ) increased, while apurinic/apyrimidinic endonuclease (APE1), one of mtBER initiators, decreased in mitochondria in the chronic phase of epileptogenesis. In conclusion, mtDNA was impaired during chronic recurrent seizures, whereas the endogenous antioxidants and the mtBER pathway failed to respond to the elevated mtDNA damage.

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Abbreviations

mtDNA:

Mitochondrial DNA

nDNA:

Nuclear DNA

OXPHOS:

Oxidative phosphorylation

SE:

Status epilepticus

SOD:

Superoxide dismutase

GSH:

Glutathione

BER:

Base excision repair

mtBER:

Mitochondrial base excision repair

ROS:

Reactive oxygen species

APE1:

Apurinic/apyrimidinic endonuclease1

polγ:

DNA polymerase γ

fpg:

Formamidopyrimidine glycosylase

Tfam:

Mitochondrial transcription factor A

SRS:

Spontaneous recurrent seizure

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Acknowledgment

This study was supported by a grant from National Natural Science Foundation of China (No. 30870838).

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Authors and Affiliations

  1. Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Youting Lin, Yuxiang Han, Lili Cao, Nanchang Xie, Xiuhe Zhao & Zhaofu Chi

  2. Department of Cadre Healthcare, Shandong Provincial Hospital, Shandong University, Jinan, China

    Jingjing Xu

  3. Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Jing Gao

  4. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, China

    Hong Jiang

  5. Department of Neurology, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Zhaofu Chi

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  1. Youting Lin
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Correspondence to Zhaofu Chi.

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Lin, Y., Han, Y., Xu, J. et al. Mitochondrial DNA Damage and the Involvement of Antioxidant Defense and Repair System in Hippocampi of Rats with Chronic Seizures. Cell Mol Neurobiol 30, 947–954 (2010). https://doi.org/10.1007/s10571-010-9524-x

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  • DOI: https://doi.org/10.1007/s10571-010-9524-x

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