Construction and characterization of a cell line deficient in repair of mitochondrial, but not nuclear, oxidative DNA damage.

研究成果: ジャーナルへの寄稿特別版

4 引用 (Scopus)

抄録

Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress. Selective accumulation of 8-oxoguanine in mitochondrial DNA in this cell line causes degradation of mitochondrial DNA followed by ATP depletion, mitochondrial membrane permeability transition, and Ca(2+) efflux, which in turn activates calpains to execute cell death. Knockdown of MUTYH which excises adenine opposite 8-oxoG in DNA prevents degradation of mitochondrial DNA and activation of calpain, thus suppressing the cell death induced by menadione.

元の言語英語
ページ(範囲)251-264
ページ数14
ジャーナルMethods in molecular biology (Clifton, N.J.)
554
DOI
出版物ステータス出版済み - 2009

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Mitochondrial DNA
DNA Damage
Cell Line
Cell Death
Calpain
Oxidative Stress
DNA Glycosylases
Vitamin K 3
Mitochondrial Membranes
Adenine
Permeability
Embryonic Structures
Complementary DNA
Fibroblasts
Adenosine Triphosphate
DNA
Genes
8-hydroxyguanine

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

これを引用

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abstract = "Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress. Selective accumulation of 8-oxoguanine in mitochondrial DNA in this cell line causes degradation of mitochondrial DNA followed by ATP depletion, mitochondrial membrane permeability transition, and Ca(2+) efflux, which in turn activates calpains to execute cell death. Knockdown of MUTYH which excises adenine opposite 8-oxoG in DNA prevents degradation of mitochondrial DNA and activation of calpain, thus suppressing the cell death induced by menadione.",
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AU - Oka, Sugako

AU - Ohno, Mizuki

AU - Nakabeppu, Yusaku

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N2 - Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress. Selective accumulation of 8-oxoguanine in mitochondrial DNA in this cell line causes degradation of mitochondrial DNA followed by ATP depletion, mitochondrial membrane permeability transition, and Ca(2+) efflux, which in turn activates calpains to execute cell death. Knockdown of MUTYH which excises adenine opposite 8-oxoG in DNA prevents degradation of mitochondrial DNA and activation of calpain, thus suppressing the cell death induced by menadione.

AB - Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress. Selective accumulation of 8-oxoguanine in mitochondrial DNA in this cell line causes degradation of mitochondrial DNA followed by ATP depletion, mitochondrial membrane permeability transition, and Ca(2+) efflux, which in turn activates calpains to execute cell death. Knockdown of MUTYH which excises adenine opposite 8-oxoG in DNA prevents degradation of mitochondrial DNA and activation of calpain, thus suppressing the cell death induced by menadione.

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