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首页> 外文期刊>Cell cycle >Novel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage
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Novel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage

机译：降低糖尿病肾细胞损伤的新型保护机制：AICAR增加NRF2 / OGG1蛋白的激活安培和降低氧化DNA损伤

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摘要

Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser792 and leads to increase the promoter activity of OGG1 through upregulation of Nrf2. Downregulation of AMPK by DN-AMPK and raptor and Nrf2 by siRNA resulted in significant decease in promoter activity and protein expression of OGG1. On the other hand, downregulation of Akt by DN-Akt and rictor by siRNA resulted in significant increase in promoter activity and protein expression of Nrf2 and OGG1. Moreover, gel shift analysis shows reduction of Nrf2 binding to OGG1 promoter in cells treated with HG while cells treated with AICAR reversed the effect of HG. Furthermore, db/db mice treated with AICAR show significant increased in AMPK and raptor phosphroylation as well as OGG1 and Nrf2 protein expression that associated with significant decrease in oxidative DNA damage (8-oxodG) compared to non-treated mice. In summary, our data provide a novel protective mechanism by which AICAR prevents renal cell damage in diabetes and the consequence complications of hyperglycemia with a specific focus on nephropathy.
机译：最近提出了在糖尿病期间暴露于肾脏细胞在糖尿病期间的高葡萄糖（Hg）涉及肾损伤。在本研究中，我们研究了AICAR治疗调节DNA修复酶，8-氧代-DNA糖基糖基酶（OGG1）在肾近端管细胞暴露于HG和DB / DB小鼠的肾脏中的潜在机制。用Hg处理的细胞2天显示OGG1启动子活性的抑制作用以及OGG1和NRF2蛋白表达。此外，AICAR的AMPK活化导致SER792增加猛禽磷酸化，并导致通过NRF2的上调增加OGG1的启动子活性。 DN-AMPK和Raptor和NRF2对AMPK的下调导致启动子活性和OGG1的蛋白表达中的显着死亡。另一方面，SiRNA的DN-AKT和RUCTOR的AKT下调导致NRF2和OGG1的启动子活性和蛋白表达显着增加。此外，凝胶移位分析显示用HG处理的细胞中对OGG1启动子的NRF2结合的降低，而AICAR处理的细胞扭转了HG的作用。此外，随着AICAR处理的DB / DB小鼠显示出AMPK和猛禽磷酸盐的显着增加，以及与未处理的小鼠相比，与氧化DNA损伤（8-OXODG）显着降低相关的OGG1和NRF2蛋白表达。总之，我们的数据提供了一种新的保护机制，通过该保护机制可以通过该保护机制可防止糖尿病中肾细胞损伤以及高血糖症的后果并发症，具有特异性关注肾病。

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  • 来源
    《Cell cycle》 |2016年第22期|共12页
  • 作者

    Habib Samy L.; Yadav Anamika; Kidane Dawit; Weiss Robert H.; Liang Sitai;

  • 作者单位

    Univ Texas Hlth Sci Ctr San Antonio Dept Cellular &

    Struct Biol San Antonio TX 78229 USA;

    Univ Texas Hlth Sci Ctr San Antonio Dept Cellular &

    Struct Biol San Antonio TX 78229 USA;

    Univ Texas Austin Coll Pharm Div Pharmacol &

    Toxicol Dell Pediat Res Inst Austin TX 78712 USA;

    Univ Calif Davis Div Nephrol Davis CA 95616 USA;

    Univ Texas Hlth Sci Ctr San Antonio Dept Cellular &

    Struct Biol San Antonio TX 78229 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    AMPK; AICAR; diabetes; mTOR; Nrf2; OGG1;

    机译：AMPK;AICAR;糖尿病;MTOR;NRF2;OGG1;

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