Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney

Kazuhiko Tsuruya, Masato Furuichi, Yohei Tominaga, Michiya Shinozaki, Masanori Tokumoto, Takahiro Yoshimitsu, Kyoichi Fukuda, Hidetoshi Kanai, Hideki Hirakata, Mitsuo Iida, Yusaku Nakabeppu

研究成果: ジャーナルへの寄稿記事

74 引用 (Scopus)

抄録

During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2′-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, 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.

元の言語英語
ページ(範囲)211-229
ページ数19
ジャーナルDNA Repair
2
発行部数2
DOI
出版物ステータス出版済み - 2 3 2003

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Reperfusion Injury
Rats
Kidney
DNA
Reperfusion
Necrosis
Ischemia
Mitochondrial DNA
Staining and Labeling
DNA Glycosylases
Messenger RNA
Kidney Medulla
Gene encoding
Kidney Cortex
High performance liquid chromatography
Ribonucleases
8-hydroxyguanine
8-oxo-7-hydrodeoxyguanosine
Assays
DNA Damage

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney. / Tsuruya, Kazuhiko; Furuichi, Masato; Tominaga, Yohei; Shinozaki, Michiya; Tokumoto, Masanori; Yoshimitsu, Takahiro; Fukuda, Kyoichi; Kanai, Hidetoshi; Hirakata, Hideki; Iida, Mitsuo; Nakabeppu, Yusaku.

:: DNA Repair, 巻 2, 番号 2, 03.02.2003, p. 211-229.

研究成果: ジャーナルへの寄稿記事

Tsuruya, K, Furuichi, M, Tominaga, Y, Shinozaki, M, Tokumoto, M, Yoshimitsu, T, Fukuda, K, Kanai, H, Hirakata, H, Iida, M & Nakabeppu, Y 2003, 'Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney', DNA Repair, 巻. 2, 番号 2, pp. 211-229. https://doi.org/10.1016/S1568-7864(02)00214-8
Tsuruya, Kazuhiko ; Furuichi, Masato ; Tominaga, Yohei ; Shinozaki, Michiya ; Tokumoto, Masanori ; Yoshimitsu, Takahiro ; Fukuda, Kyoichi ; Kanai, Hidetoshi ; Hirakata, Hideki ; Iida, Mitsuo ; Nakabeppu, Yusaku. / Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney. :: DNA Repair. 2003 ; 巻 2, 番号 2. pp. 211-229.
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abstract = "During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2′-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, 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.",
author = "Kazuhiko Tsuruya and Masato Furuichi and Yohei Tominaga and Michiya Shinozaki and Masanori Tokumoto and Takahiro Yoshimitsu and Kyoichi Fukuda and Hidetoshi Kanai and Hideki Hirakata and Mitsuo Iida and Yusaku Nakabeppu",
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T1 - Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney

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AU - Furuichi, Masato

AU - Tominaga, Yohei

AU - Shinozaki, Michiya

AU - Tokumoto, Masanori

AU - Yoshimitsu, Takahiro

AU - Fukuda, Kyoichi

AU - Kanai, Hidetoshi

AU - Hirakata, Hideki

AU - Iida, Mitsuo

AU - Nakabeppu, Yusaku

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N2 - During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2′-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, 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.

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