Mitochondrial DNA damage and the involvement of antioxidant defense and repair system in hippocampi of rats with chronic seizures.
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 polymerasegamma (polgamma) 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.
Lin
Youting
Y
Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, People's Republic of China.
Han
Yuxiang
Y
Xu
Jingjing
J
Cao
Lili
L
Gao
Jing
J
Xie
Nanchang
N
Zhao
Xiuhe
X
Jiang
Hong
H
Chi
Zhaofu
Z
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002908:Chronic Disease; D004249:DNA Damage; D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D004272:DNA, Mitochondrial; D012333:RNA, Messenger; C489030:Tfam protein, rat; D014157:Transcription Factors; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005978:Glutathione
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