Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells
Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells
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DOI：
10.3346/jkms.2011.26.11.1474
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Lee, Sang-Han
中科院分区：
文献类型：
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作者：
Lee, Yoon-Jin;Lee, Sang-Han
萝卜硫素（SFN）是一种天然存在的化合物，已知其通过Nrf 2激活诱导II相抗氧化基因，尽管其潜在机制尚未完全阐明。在这项研究中，我们研究了人支气管上皮BEAS-2B细胞中响应SFN的Nrf 2诱导，并确定了参与这一过程的信号通路。SFN处理降低细胞活力。在细胞死亡之前，在开始SFN处理的一分钟内以高速率产生细胞内活性氧（ROS）。用抗氧化剂N-乙酰半胱氨酸（NAC）预处理阻断SFN诱导的细胞生长下降。Erk 1/2在添加SFN 30分钟内被激活，而Akt磷酸化直到SFN处理后的前8小时才发生显着变化，但随后在48小时内变得显着降低。Erk 1/2磷酸化的抑制减弱了SFN诱导的细胞活力丧失。核和全细胞裂解物中的Nrf 2蛋白水平通过SFN处理增加，这依赖于ROS产生。用siRNA敲低Nrf 2减弱SFN诱导的血红素加氧酶-1（HO-1）上调。SFN处理后Nrf 2/HO-1的诱导被NAC预处理有效地抑制。总体而言，我们的研究结果表明，SFN介导的抗氧化和抗增殖反应，通过在BEAS-2B细胞中产生ROS。
Sulforaphane (SFN) is a naturally occurring compound which is known to induce the phase II antioxidant genes via Nrf2 activation, although the underlying mechanism has not been fully elucidated. In this study, we investigated Nrf2 induction in response to SFN in human bronchial epithelial BEAS-2B cells and determined the signaling pathways involved in this process. SFN treatment reduced cell viability. Prior to cell death, intracellular reactive oxygen species (ROS) were generated at a high rate within a minute of commencing SFN treatment. Pretreatment with antioxidant N-acetylcysteine (NAC) blocked SFN-induced decrease in cell growth. Erk1/2 was activated within 30 min of SFN addition, whereas Akt phosphorylation did not significantly change until the first 8 hr after SFN treatment but then became substantially low until 48 hr. Inhibition of Erk1/2 phosphorylation attenuated SFN-induced loss of cell viability. Nrf2 protein levels in both nuclear and whole cell lysates were increased by SFN treatment, which was dependent on ROS production. Knockdown of Nrf2 with siRNA attenuated SFN-induced heme oxygenase-1 (HO-1) up-regulation. Induction of the Nrf2/HO-1 after SFN treatment was potently suppressed by pretreatment with NAC. Overall, our results indicate that SFN mediates antioxidative and antiproliferative responses by generating ROS in BEAS-2B cells.