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

    研究成果: Contribution to journalArticle査読

    171 被引用数 (Scopus)

    抄録

    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.

    本文言語英語
    ページ(範囲)1588-1595
    ページ数8
    ジャーナルDiabetes
    51
    5
    DOI
    出版ステータス出版済み - 2002

    All Science Journal Classification (ASJC) codes

    • 内科学
    • 内分泌学、糖尿病および代謝内科学

    フィンガープリント

    「Accumulation of 8-hydroxy-2′-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

    引用スタイル