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

@article{Kikuchi2002ImpairmentOM,
  title={Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis},
  author={Hitoshi Kikuchi and Akiko Furuta and Kenichi Nishioka and Satoshi O. Suzuki and Yusaku Nakabeppu and Toru Iwaki},
  journal={Acta Neuropathologica},
  year={2002},
  volume={103},
  pages={408-414}
}
Abstract. Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the present 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… Expand
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Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene
TLDR
The expressions of DNA repair enzymes are predominant in spinal motor neurons, suggesting a mechanism of selective motor neuron death in this animal model of ALS and an impaired protective mechanism against oxidative stress in mitochondria. Expand
Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired by a somatic mutation found in kidney cancer.
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Immunocytochemical localisation experiments show that the G12E mutant protein has diffuse cytoplasmic distribution instead of the mitochondrial localisation found for the wild-type, providing an example of a single amino acid substitution capable of disrupting a MTS. Expand
MTH1, an Oxidized Purine Nucleoside Triphosphatase, Suppresses the Accumulation of Oxidative Damage of Nucleic Acids in the Hippocampal Microglia during Kainate-Induced Excitotoxicity
TLDR
It is shown that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity. Expand
A Role for Oxidized DNA Precursors in Huntington's Disease–Like Striatal Neurodegeneration
TLDR
The findings implicate oxidized nucleic acid precursors in the neuropathological features of Huntington's disease and identify the utilization of oxidizeducleoside triphosphates by striatal cells as a significant contributor to the pathogenesis of this disorder. Expand
MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
TLDR
It is demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons. Expand
Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis
TLDR
Evidence is provided that in this model of ALS oixidative DNA-damage is increased and base excision-repair may be deficient and free levels of 8OHG were found to be significantly higher at 120 days of age in control mice than in G93A mice. Expand
Pathological Interaction between DNA Repair and Mitochondrial Dysfunction in ALS
TLDR
Evidence supports either downregulation or impaired recruitment of DNA repair enzymes in both nuclear and mitochondrial genomes and suggests a complex metabolic dysregulation as a critical component in the promotion of the disease. Expand
Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney.
TLDR
The accumulation of 8-oxo-dG in the mitochondrial DNA rather than in nuclear DNA is likely to be involved in the pathogenic responses such as necrosis of renal tubular cells during I/R injury of the kidney, together with an altered level of OGG1 expression. Expand
Defense mechanism to oxidative DNA damage in glial cells
TLDR
Results indicate that the two repair enzymes to oxidative DNA damage are differentially regulated in glial cells, and that there is a difference in the expression of the repair enzymes between reactive astrocytes and oligodendrocyte. Expand
Variants and Polymorphisms of DNA Repair
Oxidative DNA damage is one of the earliest detectable events in several neurodegenerative diseases, often preceding the onset of the clinical symptoms. Moreover, neurons in the adult human brain can… Expand
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