Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway
Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway
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DOI：
10.1016/j.bbrc.2010.04.117
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发表时间：
2010-05-28
影响因子：
3.1
通讯作者：
Habeos, Ioannis G.
中科院分区：
文献类型：
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作者：
Chartoumpekis, Dionysios;Ziros, Panos G.;Habeos, Ioannis G.
HMG-CoA（3-羟基-3-甲基-戊二酰辅酶a）还原酶抑制剂（他汀类药物）的有益作用不仅归因于它们的降胆固醇作用，还归因于它们的多效性作用，特别是它们的抗氧化活性。Nrf2 （nf - e2相关因子2）是一种调控细胞对氧化应激源和亲电外源的转录反应的转录因子。本研究利用野生型或Nrf2敲除C57B16J小鼠和ST-2细胞的原代小鼠胚胎成纤维细胞，研究Nrf2在他汀类药物抗氧化作用中的介导作用，以及PI3K/Akt通路在这一过程中的可能参与。我们首次发现辛伐他汀通过PI3K/Akt通路激活Nrf2来降低活性氧（ROS）。(C) 2010爱思唯尔公司版权所有。
The beneficial effects of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) have been attributed not only to their cholesterol lowering effect but also to their pleiotropic actions and especially to their anti-oxidant activity. Nrf2 (NF-E2-related factor 2) is a transcription factor that orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In this study, primary mouse embryonic fibroblasts from wild type or Nrf2 knock out C57B16J mice and ST-2 cells were used to investigate the implication of Nrf2 in the mediation of the anti-oxidant effects of statins and the possible involvement of PI3K/Akt pathway in this process. We show for the first time that simvastatin lowers reactive oxygen species (ROS) by activating Nrf2 through the PI3K/Akt pathway. (C) 2010 Elsevier Inc. All rights reserved.