MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides

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Abstract

In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.

Original languageEnglish
Pages (from-to)761-772
Number of pages12
JournalDNA Repair
Volume5
Issue number7
DOIs
Publication statusPublished - Jul 13 2006

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Nucleoside-Triphosphatase
Purine Nucleosides
Purine Nucleotides
Cytotoxicity
Brain
Purines
Mitochondria
Oxidative stress
Guanosine Triphosphate
Mitochondrial DNA
Neurons
Cultured Cells
Rodentia
Oxidative Stress
Nucleotides
Genes
Adenosine Triphosphate
Cells
Genome
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides",
abstract = "In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.",
author = "Yusaku Nakabeppu and Kosuke Kajitani and Katsumi Sakamoto and hiroo yamaguchi and Daisuke Tsuchimoto",
year = "2006",
month = "7",
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doi = "10.1016/j.dnarep.2006.03.003",
language = "English",
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pages = "761--772",
journal = "DNA Repair",
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TY - JOUR

T1 - MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides

AU - Nakabeppu, Yusaku

AU - Kajitani, Kosuke

AU - Sakamoto, Katsumi

AU - yamaguchi, hiroo

AU - Tsuchimoto, Daisuke

PY - 2006/7/13

Y1 - 2006/7/13

N2 - In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.

AB - In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.

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U2 - 10.1016/j.dnarep.2006.03.003

DO - 10.1016/j.dnarep.2006.03.003

M3 - Review article

VL - 5

SP - 761

EP - 772

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

IS - 7

ER -