| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2010-08-16 |
| タイトル |
|
|
タイトル |
＜Symposium III＞Oxidative damage in brain genome and neuroprotection |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
8-oxoguanine |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
MTH1 |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
OGG1 |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
MUTYH |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
Nakabeppu, Yusaku
Sheng, Zijing
Oka, Sugako
|
| 著者所属 |
|
|
|
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University |
| 著者所属 |
|
|
|
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University |
| 著者所属 |
|
|
|
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Oxidative DNA lesions, such as 8-oxoguanine（ 8-oxoG）, accumulate in nuclear and mitochondrial genomes during aging, and such accumulation is known to dramatically increase in patient brains with Parkinson’s disease（ PD）or Alzheimer’s disease（ AD）. To counteract oxidative damage to nucleic acids, human and rodents are equipped with three distinct enzymes, MTH1, OGG1 and MUTYH. MTH1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP to their monophosphate forms. OGG1 and MUTYH are DNA glycosylases excising 8-oxoG opposite cytosine and adenine opposite 8-oxoG in DNA, respectively. We showed a signifi cant increase in 8-oxoG in cellular DNA as well as altered expression of MTH1, OGG1 and MUTYH in PD and AD brains, suggesting that the buildup of 8-oxoG may cause neurodegeneration. We have shown that buildup of 8-oxoG in either nuclear or mitochondrial DNA causes MUTYH-dependent cell death through two distinct pathways, and that accumulation of oxidized nucleotides in nucleotide pools also causes MUTYH-dependent cell death. MTH1-null mice exhibited an increased buildup of 8-oxoG in striatal mitochondrial DNA followed by more extreme neuronal dysfunction after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration, while hMTH1-transgenic mice are resistant to a mitochondrial neurotoxin, 3-nitropropionic acid （3-NP）-induced striatal degeneration, in comparison to wild-type mice. We found that doubleknockout （DKO） mice lacking OGG1 and MTH1, and to a lesser extent OGG1-KO mice, are signifi cantly sensitive to 3-NP-induced striatal degeneration, in comparison to MTH1-KO or wild-type mice, while MUTYH defi ciency increases resistance to 3-NP in OGG1-KO or wild-type background. We thus demonstrated that 8-oxoG accumulated in brain genomes causes neurodegeneration in a MUTYH-dependent manner, and which is effi ciently suppressed by MTH1 and OGG1. |
| 引用 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
弘前医学. 61(Suppl.), 2010, p.S70-S79 |
| 書誌情報 |
弘前医学
巻 61,
号 Supplement,
p. S70-S79,
発行日 2010-07-08
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0439-1721 |
| 書誌レコードID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AN00211444 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 日本十進分類法 |
|
|
主題Scheme |
NDC |
|
主題 |
490 |
| NIIサブジェクト |
|
|
主題Scheme |
Other |
|
主題 |
医学 |
| 出版者 |
|
|
出版者 |
弘前大学大学院医学研究科・弘前医学会 |
| 資源タイプ |
|
|
値 |
Article |
HirosakiMedJ_61_S70.pdf (226.9 kB)
