8-Oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts

Hiroyuki Tsutsui, Tomomi Ide, Tetsuya Shiomi, Dongchon Kang, Shunji Hayashidani, Nobuhiro Suematsu, Jing Wen, Hideo Utsumi, Naotaka Hamasaki, Akira Takeshita

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background - Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. Methods and Results - Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. Conclusions - The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

Original languageEnglish
Pages (from-to)2883-2885
Number of pages3
JournalCirculation
Volume104
Issue number24
DOIs
Publication statusPublished - Dec 11 2001

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Heart Mitochondria
DNA Damage
Oxidative Stress
Myocardial Infarction
Reactive Oxygen Species
Heart Ventricles
Mitochondria
Thiobarbituric Acid Reactive Substances
Electron Spin Resonance Spectroscopy
DNA Replication
Cardiac Myocytes
Echocardiography
Coronary Vessels
Nucleotides
Heart Failure
Western Blotting
Immunohistochemistry
8-oxodGTPase
Staining and Labeling
Antibodies

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

8-Oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts. / Tsutsui, Hiroyuki; Ide, Tomomi; Shiomi, Tetsuya; Kang, Dongchon; Hayashidani, Shunji; Suematsu, Nobuhiro; Wen, Jing; Utsumi, Hideo; Hamasaki, Naotaka; Takeshita, Akira.

In: Circulation, Vol. 104, No. 24, 11.12.2001, p. 2883-2885.

Research output: Contribution to journalArticle

Tsutsui, Hiroyuki ; Ide, Tomomi ; Shiomi, Tetsuya ; Kang, Dongchon ; Hayashidani, Shunji ; Suematsu, Nobuhiro ; Wen, Jing ; Utsumi, Hideo ; Hamasaki, Naotaka ; Takeshita, Akira. / 8-Oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts. In: Circulation. 2001 ; Vol. 104, No. 24. pp. 2883-2885.
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T1 - 8-Oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts

AU - Tsutsui, Hiroyuki

AU - Ide, Tomomi

AU - Shiomi, Tetsuya

AU - Kang, Dongchon

AU - Hayashidani, Shunji

AU - Suematsu, Nobuhiro

AU - Wen, Jing

AU - Utsumi, Hideo

AU - Hamasaki, Naotaka

AU - Takeshita, Akira

PY - 2001/12/11

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N2 - Background - Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. Methods and Results - Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. Conclusions - The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

AB - Background - Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. Methods and Results - Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. Conclusions - The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

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