Mitochondrial base excision repair pathway failed to respond to status epilepticus induced by pilocarpine.
Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as an important mechanism underlying mitochondrial deficiency in epileptic seizures. In focusing on the role of the DNA repair pathway, we determined the response of the mitochondrial base excision repair (mtBER) pathway in pilocarpine-induced status epilepticus (SE) in hippocampi of male Wistar rats. The expression of 8-oxoguanine DNA glycosylase (OGG1) and polymerase gamma (polgamma) was decreased at both the cellular mRNA and mitochondrial protein levels at 3, 9 and 25h after the onset of SE. The mRNA and protein levels of APE1 were maintained, but the mitochondrial protein level decreased at 3 and 9h and recovered at 25h. Therefore, the mtBER pathway failed to respond to SE induced by pilocarpine. The failure of mitochondrial import might be an important factor responsible for the lowered mtBER enzymes in mitochondria. We hypothesize that the down-regulation of mtBER enzymes may aggravate mtDNA damage and mitochondrial deficiency after the onset of SE.
Lin
Youting
Y
Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan 250012, PR China.
Xu
Jingjing
J
Cao
Lili
L
Han
Yuxiang
Y
Gao
Jing
J
Xie
Nanchang
N
Zhao
Xiuhe
X
Jiang
Hong
H
Chi
Zhaofu
Z
D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics; D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D010862:Pilocarpine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D010862:Pilocarpine; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase