title: Mitochondrial DNA damage and the involvement of antioxidant defense and repair system in hippocampi of rats with chronic seizures.
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 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.
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, People's Republic of China.
authors.forename: Youting
authors.initials: Y
authors.lastname: Lin
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Han
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xu
authors.forename: Lili
authors.initials: L
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Nanchang
authors.initials: N
authors.lastname: Xie
authors.forename: Xiuhe
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhaofu
authors.initials: Z
authors.lastname: Chi
mesh_terms: 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
chemical_list: 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
references.citation: Gene. 2002 Mar 6;286(1):127-34
references.pmid: 11943468
references.citation: Biochem Soc Symp. 1995;61:1-31
references.pmid: 8660387
references.citation: Ann Neurol. 2000 Nov;48(5):766-73
references.pmid: 11079540
references.citation: J Biol Chem. 2003 Oct 10;278(41):39951-9
references.pmid: 12882965
references.citation: Epilepsy Res. 2006 Mar;68(3):229-39
references.pmid: 16337777
references.citation: Epilepsy Res. 2002 Feb;48(3):157-68
references.pmid: 11904234
references.citation: Biochim Biophys Acta. 2006 May-Jun;1763(5-6):473-81
references.pmid: 16624428
references.citation: Neurosci Lett. 2004 Jan 30;355(3):231-5
references.pmid: 14732473
references.citation: J Clin Invest. 2004 Jun;113(12):1711-21
references.pmid: 15199406
references.citation: Free Radic Biol Med. 2004 Mar 1;36(5):542-54
references.pmid: 14980699
references.citation: Hippocampus. 2005;15(8):1057-71
references.pmid: 16216017
references.citation: J Neurochem. 2004 Feb;88(3):513-31
references.pmid: 14720201
references.citation: DNA Repair (Amst). 2004 Jun 3;3(6):617-27
references.pmid: 15135729
references.citation: J Cell Physiol. 2002 Nov;193(2):180-6
references.pmid: 12384995
references.citation: Neuroscience. 2007 Apr 14;145(4):1187-200
references.pmid: 16934943
references.citation: Pflugers Arch. 2000;440(5 Suppl):R160-2
references.pmid: 11005654
references.citation: Mitochondrion. 2005 Apr;5(2):89-108
references.pmid: 16050976
references.citation: Nat Genet. 2001 Jul;28(3):272-5
references.pmid: 11431699
references.citation: J Neurosci Methods. 2008 Jul 30;172(2):143-57
references.pmid: 18550176
references.citation: Mitochondrion. 2002 Nov;2(1-2):59-70
references.pmid: 16120309
references.citation: Brain Res Mol Brain Res. 2001 Mar 5;87(2):257-62
references.pmid: 11245929
references.citation: Nucleic Acids Res. 2005 Aug 17;33(14):4660-71
references.pmid: 16107556
references.citation: Neurosci Lett. 2007 Jan 10;411(2):152-7
references.pmid: 17092649
references.citation: Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):311-22
references.pmid: 15197331
references.citation: J Neurochem. 2001 Jul;78(1):141-54
references.pmid: 11432981
references.citation: Eur J Neurosci. 2002 Apr;15(7):1105-14
references.pmid: 11982622
references.citation: Biochimie. 2003 Nov;85(11):1053-71
references.pmid: 14726013
references.citation: Brain Res. 1996 Jul 15;727(1-2):133-44
references.pmid: 8842391
references.citation: Exp Neurol. 2005 Mar;192(1):79-88
references.pmid: 15698621
references.citation: Biochemistry. 1999 Jan 5;38(1):459-64
references.pmid: 9890929
references.citation: Brain Res Mol Brain Res. 1997 Feb;44(1):167-70
references.pmid: 9030714
references.citation: Epilepsia. 2004 Oct;45(10):1202-9
references.pmid: 15461674
references.citation: J Neurochem. 2000 Mar;74(3):1098-105
references.pmid: 10693941
references.citation: Methods Mol Biol. 2002;196:155-62
references.pmid: 12152194
references.citation: Neuroscience. 2007 Apr 14;145(4):1330-40
references.pmid: 17156934
references.citation: Neurobiol Aging. 2006 Aug;27(8):1129-36
references.pmid: 16005114
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references.pmid: 4110397
references.citation: Nature. 2004 Jun 24;429(6994):883-91
references.pmid: 15190254
references.citation: Nucleic Acids Res. 2006 Apr 14;34(7):2067-76
references.pmid: 16617147
references.citation: Science. 1992 May 1;256(5057):628-32
references.pmid: 1533953
references.citation: Brain Res. 2005 May 3;1042(2):236-40
references.pmid: 15854596
references.citation: Mutat Res. 2001 Mar 7;485(2):143-52
references.pmid: 11182545
references.citation: J Neurosci Res. 1998 Nov 1;54(3):382-9
references.pmid: 9819143
references.citation: J Neurochem. 2008 Aug;106(3):1044-51
references.pmid: 18466343
references.citation: Lab Invest. 1993 Sep;69(3):261-74
references.pmid: 8377469
references.citation: Neurobiol Dis. 2008 Apr;30(1):130-8
references.pmid: 18295498
references.citation: J Neurosci Res. 2000 Jul 15;61(2):225-36
references.pmid: 10878595
references.citation: Cancer Res. 2003 Feb 1;63(3):608-15
references.pmid: 12566303