Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells.
Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells.
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白藜芦醇在人类T细胞中，AMP激活的蛋白激酶在铁蛋白H基因表达中的作用。
DOI：
10.1021/bi400399f
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发表时间：
2013-07-30
期刊：
影响因子：
2.9
通讯作者：
Tsuji, Yoshiaki
中科院分区：
文献类型：
--
作者：
Iwasaki, Kenta;Ray, Paul D.;Huang, Bo-Wen;Sakamoto, Kensuke;Kobayashi, Takaaki;Tsuji, Yoshiaki
白藜芦醇是一种天然多酚，通过抗氧化反应元件 (ARE) 诱导一系列细胞保护基因的表达，从而提高细胞抗氧化能力。然而，白藜芦醇引发的上游信号事件导致 ARE 增强子激活，特别是在免疫细胞中，尚未完全阐明。在本研究中，在 Jurkat T 细胞和人外周血单核细胞中进一步研究了白藜芦醇对铁蛋白重链（铁蛋白 H）基因的 ARE 依赖性转录激活。我们发现 AMP 激活蛋白激酶 (AMPK) 在白藜芦醇激活核因子 E2 相关因子 (Nrf2) 以及随后的 ARE 依赖性铁蛋白 H 基因转录中发挥关键作用。用 siRNA 敲低 AMPKα 后对 Nrf2 进行染色质免疫沉淀测定，结果显示 Nrf2 核积累以及随后与白藜芦醇诱导的铁蛋白 H ARE 的结合依赖于 AMPKα 的激活，而不是 PI3K/AKT。此外，AMPKα 敲低阻断了白藜芦醇诱导的糖原合酶激酶 3β (GSK3β) Ser9 磷酸化以及铁蛋白 H 和 HO-1 基因的 ARE 依赖性转录激活，表明 AMPKα 是 GSK3β 磷酸化和 Nrf2-ARE 途径激活的上游激酶。一致地，siRNA 敲低 GSK3β 增强了白藜芦醇介导的铁蛋白 H mRNA 诱导，而化合物 C 或 siRNA 抑制 AMPKα 减弱了白藜芦醇对 CD3+ T 细胞中氧化应激诱导的细胞毒性的保护作用。总的来说，这些结果表明 AMPKα 在白藜芦醇对铁蛋白 H 基因的 ARE 依赖性转录中发挥着重要作用，并可能影响免疫细胞中的氧化还原状态。
Resveratrol, a natural polyphenol, increases cellular antioxidant capacity by inducing the expression of a battery of cytoprotective genes through an antioxidant responsive element (ARE). However, upstream signaling events initiated by resveratrol leading to the activation of an ARE enhancer, particularly in immune cells, have not been fully elucidated. In this study, ARE-dependent transcriptional activation of ferritin heavy chain (ferritin H) gene by resveratrol was further investigated in Jurkat T cells and human peripheral blood mononuclear cells. We found that AMP-activated protein kinase (AMPK) plays a key role in the activation of nuclear factor E2-related factor (Nrf2) and subsequent ARE-dependent ferritin H gene transcription by resveratrol. Chromatin immunoprecipitation assay for Nrf2 after AMPKα knockdown with siRNA revealed that Nrf2 nuclear accumulation and subsequent binding to the ferritin H ARE induced by resveratrol was dependent on activation of AMPKα, but not PI3K/AKT. Furthermore, AMPKα knockdown blocked resveratrol-induced phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser9 as well as ARE-dependent transcriptional activation of the ferritin H and HO-1 genes, suggesting that AMPKα is an upstream kinase for GSK3β phosphorylation and activation of the Nrf2-ARE pathway. Consistently, GSK3β knockdown by siRNA enhanced resveratrol-mediated ferritin H mRNA induction, and the inhibition of AMPKα by compound C or siRNA diminished the protective effect of resveratrol against oxidative stress-induced cytotoxicity in CD3+ T cells. Collectively, these results suggest that AMPKα plays a significant role in ARE-dependent transcription of ferritin H genes by resveratrol and may influence the redox status in immune cells.
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影响因子：
4.8
作者：
Ferreira, C;Bucchini, D;Beaumont, C
通讯作者：
Beaumont, C
影响因子：
4.8
作者：
Lee, Jung Yeon;Choi, A-Young;Kang, Insug
通讯作者：
Kang, Insug
DOI：
10.1073/pnas.94.25.14138
发表时间：
1997-12-09
影响因子：
11.1
作者：
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通讯作者：
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5.8
作者：
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通讯作者：
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影响因子：
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作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
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