MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity

研究成果: ジャーナルへの寄稿記事

50 引用 (Scopus)

抄録

Enhanced oxidative stress has been implicated in the excitotoxicity of the CNS, and 8-oxo-7,8-dihydro-guanine (8-oxoG), a major type of oxidative damage in nucleic acids, was reported to be accumulated in the rat hippocampus after kainate administration. We herein showed that the 8-oxoG levels in mitochondrial DNA and cellular RNA increased significantly in the CA3 subregion of the mouse hippocampus 6-12 h after kainate administration but returned to basal levels within a few days. Laser-scanning confocal microscopy revealed the 8-oxoG accumulation in mitochondrialDNAto be remarkable inCA3microglia, whereas that in nuclearDNAor cellularRNA was also detected in the CA3 pyramidal cells and astrocytes. 8-oxoG accumulation in cellularDNAor RNA should be suppressed by MutT homolog 1 (MTH1) with 8-oxo-dGTPase (8-oxo-7,8-dihydro-2′- deoxyguanosine triphosphatase) activity and 8-oxoG-DNA glycosylase 1 (OGG1) with 8-oxoG DNA glycosylase activity. We thus examined the expression level of MTH1 and OGG1 in the mouse hippocampus after kainate administration. The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increasedMTH1protein level was observed, whereas the Ogg1mRNAlevel remained constant. MTH1-null and wild-type mice exhibited a similar degree of CA3 neuron loss after kainate administration; however, the 8-oxoG levels that accumulated in mitochondrial DNA and cellular RNA in the CA3 microglia significantly increased in the MTH1-null mice in comparison with wild-type mice, thus demonstrating that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.

元の言語英語
ページ(範囲)1688-1698
ページ数11
ジャーナルJournal of Neuroscience
26
発行部数6
DOI
出版物ステータス出版済み - 2 8 2006

Fingerprint

Nucleoside-Triphosphatase
Purine Nucleosides
Kainic Acid
Guanine
Microglia
Nucleic Acids
DNA Glycosylases
Hippocampus
RNA
Mitochondrial DNA
Pyramidal Cells
Confocal Microscopy
Astrocytes
Oxidative Stress
Neurons
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

@article{b4ecaaf4b39d43efae04a2c459c6728e,
title = "MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity",
abstract = "Enhanced oxidative stress has been implicated in the excitotoxicity of the CNS, and 8-oxo-7,8-dihydro-guanine (8-oxoG), a major type of oxidative damage in nucleic acids, was reported to be accumulated in the rat hippocampus after kainate administration. We herein showed that the 8-oxoG levels in mitochondrial DNA and cellular RNA increased significantly in the CA3 subregion of the mouse hippocampus 6-12 h after kainate administration but returned to basal levels within a few days. Laser-scanning confocal microscopy revealed the 8-oxoG accumulation in mitochondrialDNAto be remarkable inCA3microglia, whereas that in nuclearDNAor cellularRNA was also detected in the CA3 pyramidal cells and astrocytes. 8-oxoG accumulation in cellularDNAor RNA should be suppressed by MutT homolog 1 (MTH1) with 8-oxo-dGTPase (8-oxo-7,8-dihydro-2′- deoxyguanosine triphosphatase) activity and 8-oxoG-DNA glycosylase 1 (OGG1) with 8-oxoG DNA glycosylase activity. We thus examined the expression level of MTH1 and OGG1 in the mouse hippocampus after kainate administration. The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increasedMTH1protein level was observed, whereas the Ogg1mRNAlevel remained constant. MTH1-null and wild-type mice exhibited a similar degree of CA3 neuron loss after kainate administration; however, the 8-oxoG levels that accumulated in mitochondrial DNA and cellular RNA in the CA3 microglia significantly increased in the MTH1-null mice in comparison with wild-type mice, thus demonstrating that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.",
author = "Kosuke Kajitani and hiroo yamaguchi and Yukihiko Dan and Masato Furuichi and Dongchon Kang and Yusaku Nakabeppu",
year = "2006",
month = "2",
day = "8",
doi = "10.1523/JNEUROSCI.4948-05.2006",
language = "English",
volume = "26",
pages = "1688--1698",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",

}

TY - JOUR

T1 - MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity

AU - Kajitani, Kosuke

AU - yamaguchi, hiroo

AU - Dan, Yukihiko

AU - Furuichi, Masato

AU - Kang, Dongchon

AU - Nakabeppu, Yusaku

PY - 2006/2/8

Y1 - 2006/2/8

N2 - Enhanced oxidative stress has been implicated in the excitotoxicity of the CNS, and 8-oxo-7,8-dihydro-guanine (8-oxoG), a major type of oxidative damage in nucleic acids, was reported to be accumulated in the rat hippocampus after kainate administration. We herein showed that the 8-oxoG levels in mitochondrial DNA and cellular RNA increased significantly in the CA3 subregion of the mouse hippocampus 6-12 h after kainate administration but returned to basal levels within a few days. Laser-scanning confocal microscopy revealed the 8-oxoG accumulation in mitochondrialDNAto be remarkable inCA3microglia, whereas that in nuclearDNAor cellularRNA was also detected in the CA3 pyramidal cells and astrocytes. 8-oxoG accumulation in cellularDNAor RNA should be suppressed by MutT homolog 1 (MTH1) with 8-oxo-dGTPase (8-oxo-7,8-dihydro-2′- deoxyguanosine triphosphatase) activity and 8-oxoG-DNA glycosylase 1 (OGG1) with 8-oxoG DNA glycosylase activity. We thus examined the expression level of MTH1 and OGG1 in the mouse hippocampus after kainate administration. The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increasedMTH1protein level was observed, whereas the Ogg1mRNAlevel remained constant. MTH1-null and wild-type mice exhibited a similar degree of CA3 neuron loss after kainate administration; however, the 8-oxoG levels that accumulated in mitochondrial DNA and cellular RNA in the CA3 microglia significantly increased in the MTH1-null mice in comparison with wild-type mice, thus demonstrating that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.

AB - Enhanced oxidative stress has been implicated in the excitotoxicity of the CNS, and 8-oxo-7,8-dihydro-guanine (8-oxoG), a major type of oxidative damage in nucleic acids, was reported to be accumulated in the rat hippocampus after kainate administration. We herein showed that the 8-oxoG levels in mitochondrial DNA and cellular RNA increased significantly in the CA3 subregion of the mouse hippocampus 6-12 h after kainate administration but returned to basal levels within a few days. Laser-scanning confocal microscopy revealed the 8-oxoG accumulation in mitochondrialDNAto be remarkable inCA3microglia, whereas that in nuclearDNAor cellularRNA was also detected in the CA3 pyramidal cells and astrocytes. 8-oxoG accumulation in cellularDNAor RNA should be suppressed by MutT homolog 1 (MTH1) with 8-oxo-dGTPase (8-oxo-7,8-dihydro-2′- deoxyguanosine triphosphatase) activity and 8-oxoG-DNA glycosylase 1 (OGG1) with 8-oxoG DNA glycosylase activity. We thus examined the expression level of MTH1 and OGG1 in the mouse hippocampus after kainate administration. The Mth1 mRNA level decreased soon after kainate administration and then quickly recovered beyond the basal level, and a continuously increasedMTH1protein level was observed, whereas the Ogg1mRNAlevel remained constant. MTH1-null and wild-type mice exhibited a similar degree of CA3 neuron loss after kainate administration; however, the 8-oxoG levels that accumulated in mitochondrial DNA and cellular RNA in the CA3 microglia significantly increased in the MTH1-null mice in comparison with wild-type mice, thus demonstrating that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.

UR - http://www.scopus.com/inward/record.url?scp=32544458774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32544458774&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.4948-05.2006

DO - 10.1523/JNEUROSCI.4948-05.2006

M3 - Article

VL - 26

SP - 1688

EP - 1698

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 6

ER -