Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats

Maiko Kakimoto, Toyoshi Inoguchi, Toshiyo Sonta, Hai Yan Yu, Minako Imamura, Takashi Etoh, Toshihiko Hashimoto, Hajime Nawata

    Research output: Contribution to journalArticle

    153 Citations (Scopus)

    Abstract

    Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the onset of diabetes, levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a marker of oxidative DNA damage, were significantly increased in mtDNA from kidney of diabetic rats but not in nuclear DNA, suggesting the predominant damage of mtDNA. Semiquantitative analysis using PCR showed that the frequency of 4,834-bp deleted mtDNA was markedly increased in kidney of diabetic rats at 8 weeks, but it did not change at 4 weeks. Intervention by insulin treatment starting at 8 weeks rapidly normalized an increase in renal 8-OHdG levels of diabetic rats, but it did not reverse an increase in the frequency of deleted mtDNA. Our study demonstrated for the first time that oxidative mtDNA damage and subsequent mtDNA deletion may be accumulated in kidney of diabetic rats. This may be involved in the pathogenesis of diabetic nephropathy.

    Original languageEnglish
    Pages (from-to)1588-1595
    Number of pages8
    JournalDiabetes
    Volume51
    Issue number5
    DOIs
    Publication statusPublished - Jan 1 2002

    Fingerprint

    Mitochondrial DNA
    Kidney
    DNA Damage
    Diabetic Nephropathies
    8-oxo-7-hydrodeoxyguanosine
    Streptozocin
    Oxidative Stress
    Insulin
    Polymerase Chain Reaction
    DNA

    All Science Journal Classification (ASJC) codes

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Kakimoto, M., Inoguchi, T., Sonta, T., Yu, H. Y., Imamura, M., Etoh, T., ... Nawata, H. (2002). Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats. Diabetes, 51(5), 1588-1595. https://doi.org/10.2337/diabetes.51.5.1588

    Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats. / Kakimoto, Maiko; Inoguchi, Toyoshi; Sonta, Toshiyo; Yu, Hai Yan; Imamura, Minako; Etoh, Takashi; Hashimoto, Toshihiko; Nawata, Hajime.

    In: Diabetes, Vol. 51, No. 5, 01.01.2002, p. 1588-1595.

    Research output: Contribution to journalArticle

    Kakimoto, M, Inoguchi, T, Sonta, T, Yu, HY, Imamura, M, Etoh, T, Hashimoto, T & Nawata, H 2002, 'Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats', Diabetes, vol. 51, no. 5, pp. 1588-1595. https://doi.org/10.2337/diabetes.51.5.1588
    Kakimoto, Maiko ; Inoguchi, Toyoshi ; Sonta, Toshiyo ; Yu, Hai Yan ; Imamura, Minako ; Etoh, Takashi ; Hashimoto, Toshihiko ; Nawata, Hajime. / Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats. In: Diabetes. 2002 ; Vol. 51, No. 5. pp. 1588-1595.
    @article{f84f459281794ac9baa921f5e078bc04,
    title = "Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats",
    abstract = "Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the onset of diabetes, levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a marker of oxidative DNA damage, were significantly increased in mtDNA from kidney of diabetic rats but not in nuclear DNA, suggesting the predominant damage of mtDNA. Semiquantitative analysis using PCR showed that the frequency of 4,834-bp deleted mtDNA was markedly increased in kidney of diabetic rats at 8 weeks, but it did not change at 4 weeks. Intervention by insulin treatment starting at 8 weeks rapidly normalized an increase in renal 8-OHdG levels of diabetic rats, but it did not reverse an increase in the frequency of deleted mtDNA. Our study demonstrated for the first time that oxidative mtDNA damage and subsequent mtDNA deletion may be accumulated in kidney of diabetic rats. This may be involved in the pathogenesis of diabetic nephropathy.",
    author = "Maiko Kakimoto and Toyoshi Inoguchi and Toshiyo Sonta and Yu, {Hai Yan} and Minako Imamura and Takashi Etoh and Toshihiko Hashimoto and Hajime Nawata",
    year = "2002",
    month = "1",
    day = "1",
    doi = "10.2337/diabetes.51.5.1588",
    language = "English",
    volume = "51",
    pages = "1588--1595",
    journal = "Diabetes",
    issn = "0012-1797",
    publisher = "医学出版",
    number = "5",

    }

    TY - JOUR

    T1 - Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats

    AU - Kakimoto, Maiko

    AU - Inoguchi, Toyoshi

    AU - Sonta, Toshiyo

    AU - Yu, Hai Yan

    AU - Imamura, Minako

    AU - Etoh, Takashi

    AU - Hashimoto, Toshihiko

    AU - Nawata, Hajime

    PY - 2002/1/1

    Y1 - 2002/1/1

    N2 - Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the onset of diabetes, levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a marker of oxidative DNA damage, were significantly increased in mtDNA from kidney of diabetic rats but not in nuclear DNA, suggesting the predominant damage of mtDNA. Semiquantitative analysis using PCR showed that the frequency of 4,834-bp deleted mtDNA was markedly increased in kidney of diabetic rats at 8 weeks, but it did not change at 4 weeks. Intervention by insulin treatment starting at 8 weeks rapidly normalized an increase in renal 8-OHdG levels of diabetic rats, but it did not reverse an increase in the frequency of deleted mtDNA. Our study demonstrated for the first time that oxidative mtDNA damage and subsequent mtDNA deletion may be accumulated in kidney of diabetic rats. This may be involved in the pathogenesis of diabetic nephropathy.

    AB - Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the onset of diabetes, levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a marker of oxidative DNA damage, were significantly increased in mtDNA from kidney of diabetic rats but not in nuclear DNA, suggesting the predominant damage of mtDNA. Semiquantitative analysis using PCR showed that the frequency of 4,834-bp deleted mtDNA was markedly increased in kidney of diabetic rats at 8 weeks, but it did not change at 4 weeks. Intervention by insulin treatment starting at 8 weeks rapidly normalized an increase in renal 8-OHdG levels of diabetic rats, but it did not reverse an increase in the frequency of deleted mtDNA. Our study demonstrated for the first time that oxidative mtDNA damage and subsequent mtDNA deletion may be accumulated in kidney of diabetic rats. This may be involved in the pathogenesis of diabetic nephropathy.

    UR - http://www.scopus.com/inward/record.url?scp=0036317040&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0036317040&partnerID=8YFLogxK

    U2 - 10.2337/diabetes.51.5.1588

    DO - 10.2337/diabetes.51.5.1588

    M3 - Article

    C2 - 11978660

    AN - SCOPUS:0036317040

    VL - 51

    SP - 1588

    EP - 1595

    JO - Diabetes

    JF - Diabetes

    SN - 0012-1797

    IS - 5

    ER -