Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis

Hitoshi Kikuchi, Akiko Furuta, Ken Ichi Nishioka, Satoshi Suzuki, Yusaku Nakabeppu, Toru Iwaki

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the presen study, we investigated the expression of two major human enzymes that prevent errors caused by 8-oxoguanine (8-oxoG), a mitochondrial form of 8-oxoG DNA glycosylase (hOGG1) and oxidized purine nucleoside triphosphatase (hMTH1). We also investigated the relationship between their expression and the 8-oxoG accumulation observed in the large motor neurons of the lumbar spinal cord in seven cases of adult onset sporadic ALS, four cases of subarachnoid hemorrhage (SAH) and four control cases. 8-oxoG immunoreactivity increased in most large motor neurons in both the ALS and SAH cases. However, the large motor neurons in the control cases often lacked hOGG1 immunoreactivity, although some neurons expressed hOGG1 in either homogeneous or fine granular patterns. In SAH cases, most large motor neurons showed a fine granular pattern proportional to the increased 8-oxoG immunoreactivity. However, only half of the remaining motor neurons in ALS expressed hOGG1 in the fine granular pattern, and the rest did not show any immunoreactivity. In addition, small aggregates of hMTH1 in the nuclei of the anterior horn cells were present in several ALS cases. Our results indicate that the oxidative damage accumulates in the mitochondria of motor neurons in ALS, and that hOGG1 does not repair the damage efficiently, which may lead to a loss of motor neurons in ALS.

Original languageEnglish
Pages (from-to)408-414
Number of pages7
JournalActa neuropathologica
Volume103
Issue number4
DOIs
Publication statusPublished - Dec 1 2002

Fingerprint

DNA Repair Enzymes
Amyotrophic Lateral Sclerosis
Guanine
Motor Neurons
Mitochondrial DNA
Subarachnoid Hemorrhage
Spinal Cord
Nucleoside-Triphosphatase
Anterior Horn Cells
DNA Glycosylases
Purine Nucleosides
Mitochondria
Oxidative Stress
Neurons
Enzymes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis. / Kikuchi, Hitoshi; Furuta, Akiko; Nishioka, Ken Ichi; Suzuki, Satoshi; Nakabeppu, Yusaku; Iwaki, Toru.

In: Acta neuropathologica, Vol. 103, No. 4, 01.12.2002, p. 408-414.

Research output: Contribution to journalArticle

@article{9b939d34fc0447cdafa52e94ab4d1f5d,
title = "Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis",
abstract = "Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the presen study, we investigated the expression of two major human enzymes that prevent errors caused by 8-oxoguanine (8-oxoG), a mitochondrial form of 8-oxoG DNA glycosylase (hOGG1) and oxidized purine nucleoside triphosphatase (hMTH1). We also investigated the relationship between their expression and the 8-oxoG accumulation observed in the large motor neurons of the lumbar spinal cord in seven cases of adult onset sporadic ALS, four cases of subarachnoid hemorrhage (SAH) and four control cases. 8-oxoG immunoreactivity increased in most large motor neurons in both the ALS and SAH cases. However, the large motor neurons in the control cases often lacked hOGG1 immunoreactivity, although some neurons expressed hOGG1 in either homogeneous or fine granular patterns. In SAH cases, most large motor neurons showed a fine granular pattern proportional to the increased 8-oxoG immunoreactivity. However, only half of the remaining motor neurons in ALS expressed hOGG1 in the fine granular pattern, and the rest did not show any immunoreactivity. In addition, small aggregates of hMTH1 in the nuclei of the anterior horn cells were present in several ALS cases. Our results indicate that the oxidative damage accumulates in the mitochondria of motor neurons in ALS, and that hOGG1 does not repair the damage efficiently, which may lead to a loss of motor neurons in ALS.",
author = "Hitoshi Kikuchi and Akiko Furuta and Nishioka, {Ken Ichi} and Satoshi Suzuki and Yusaku Nakabeppu and Toru Iwaki",
year = "2002",
month = "12",
day = "1",
doi = "10.1007/s00401-001-0480-x",
language = "English",
volume = "103",
pages = "408--414",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis

AU - Kikuchi, Hitoshi

AU - Furuta, Akiko

AU - Nishioka, Ken Ichi

AU - Suzuki, Satoshi

AU - Nakabeppu, Yusaku

AU - Iwaki, Toru

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the presen study, we investigated the expression of two major human enzymes that prevent errors caused by 8-oxoguanine (8-oxoG), a mitochondrial form of 8-oxoG DNA glycosylase (hOGG1) and oxidized purine nucleoside triphosphatase (hMTH1). We also investigated the relationship between their expression and the 8-oxoG accumulation observed in the large motor neurons of the lumbar spinal cord in seven cases of adult onset sporadic ALS, four cases of subarachnoid hemorrhage (SAH) and four control cases. 8-oxoG immunoreactivity increased in most large motor neurons in both the ALS and SAH cases. However, the large motor neurons in the control cases often lacked hOGG1 immunoreactivity, although some neurons expressed hOGG1 in either homogeneous or fine granular patterns. In SAH cases, most large motor neurons showed a fine granular pattern proportional to the increased 8-oxoG immunoreactivity. However, only half of the remaining motor neurons in ALS expressed hOGG1 in the fine granular pattern, and the rest did not show any immunoreactivity. In addition, small aggregates of hMTH1 in the nuclei of the anterior horn cells were present in several ALS cases. Our results indicate that the oxidative damage accumulates in the mitochondria of motor neurons in ALS, and that hOGG1 does not repair the damage efficiently, which may lead to a loss of motor neurons in ALS.

AB - Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the presen study, we investigated the expression of two major human enzymes that prevent errors caused by 8-oxoguanine (8-oxoG), a mitochondrial form of 8-oxoG DNA glycosylase (hOGG1) and oxidized purine nucleoside triphosphatase (hMTH1). We also investigated the relationship between their expression and the 8-oxoG accumulation observed in the large motor neurons of the lumbar spinal cord in seven cases of adult onset sporadic ALS, four cases of subarachnoid hemorrhage (SAH) and four control cases. 8-oxoG immunoreactivity increased in most large motor neurons in both the ALS and SAH cases. However, the large motor neurons in the control cases often lacked hOGG1 immunoreactivity, although some neurons expressed hOGG1 in either homogeneous or fine granular patterns. In SAH cases, most large motor neurons showed a fine granular pattern proportional to the increased 8-oxoG immunoreactivity. However, only half of the remaining motor neurons in ALS expressed hOGG1 in the fine granular pattern, and the rest did not show any immunoreactivity. In addition, small aggregates of hMTH1 in the nuclei of the anterior horn cells were present in several ALS cases. Our results indicate that the oxidative damage accumulates in the mitochondria of motor neurons in ALS, and that hOGG1 does not repair the damage efficiently, which may lead to a loss of motor neurons in ALS.

UR - http://www.scopus.com/inward/record.url?scp=0036946576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036946576&partnerID=8YFLogxK

U2 - 10.1007/s00401-001-0480-x

DO - 10.1007/s00401-001-0480-x

M3 - Article

VL - 103

SP - 408

EP - 414

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 4

ER -