Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells
Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells
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DOI：
10.1016/j.nutres.2015.09.018
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发表时间：
2016-02-01
影响因子：
4.5
通讯作者：
Morihara, Naoaki
中科院分区：
文献类型：
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作者：
Hiramatsu, Kei;Tsuneyoshi, Tadamitsu;Morihara, Naoaki
核因子红细胞2相关因子2（Nrf 2）-抗氧化反应元件（ARE）通路保护细胞免受氧化应激并调节细胞氧化还原平衡。这一途径的激活会诱导多种抗氧化酶，从而保护我们的身体免受氧化损伤。据报道，老化大蒜提取物（AGE），一种富含水溶性半胱氨酰部分的大蒜制剂，可降低氧化应激，有助于改善心血管、肾脏和肝脏疾病。我们假设AGE通过Nrf 2-ARE途径增强培养的人脐静脉内皮细胞中抗氧化酶的表达。抗氧化酶的基因表达采用实时聚合酶链反应测定。核积累的Nrf 2和抗氧化酶的表达进行了评估，使用蛋白质印迹分析。我们发现AGE以时间和剂量依赖的方式促进Nrf 2向细胞核的积累，并增加血红素加氧酶-1（HO-1）和谷氨酸-半胱氨酸连接酶修饰亚基（GCLM）的基因表达和多肽水平。此外，在人脐静脉内皮细胞中，发现AGE在升高HO-1和GCLM的基因表达中的作用是通过Nrf 2活化介导的。综上所述，这些观察结果表明，AGE通过激活Nrf 2-ARE信号通路诱导抗氧化酶HO-1和GCLM的表达。(C)2016 Elsevier Inc. All rights reserved.
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway defends cells against oxidative stress and regulates the cellular redox balance. Activation of this pathway induces a variety of antioxidant enzymes, resulting in the protection of our bodies against oxidative damage. It has been reported that aged garlic extract (AGE), a garlic preparation that is rich in water-soluble cysteinyl moieties, reduces oxidative stress and helps to ameliorate of cardiovascular, renal and hepatic diseases. We hypothesized that AGE enhances the expression of antioxidant enzymes via the Nrf2-ARE pathway in human umbilical vein endothelial cells in culture. Gene expression of antioxidant enzymes was measured using real-time polymerase chain reaction. Nuclear accumulation of Nrf2 and antioxidant enzymes expression were evaluated using western blotting analyses. We found that AGE promoted the accumulation of Nrf2 into the nucleus in a time- and dose-dependent manner and increased the gene expression and polypeptide level of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM). Moreover, the effect of AGE in elevating the gene expression of HO-1 and GCLM was found to be mediated via Nrf2 activation in human umbilical vein endothelial cells. Taken together, these observations suggest that AGE induces the expression of HO-1 and GCLM, which are antioxidant enzymes, via activation of the Nrf2-ARE signaling pathway. (C) 2016 Elsevier Inc. All rights reserved.