Fucoxanthin enhances the level of reduced glutathione via the Nrf2-mediated pathway in human keratinocytes.
Fucoxanthin enhances the level of reduced glutathione via the Nrf2-mediated pathway in human keratinocytes.
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DOI：
10.3390/md12074214
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发表时间：
2014-07-15
期刊：
影响因子：
5.4
通讯作者：
Hyun JW
中科院分区：
文献类型：
--
作者：
Zheng J;Piao MJ;Kim KC;Yao CW;Cha JW;Hyun JW
岩藻黄素是一种天然的类胡萝卜素，在海藻中含量丰富，具有抗氧化作用。本研究探讨了岩藻黄质在诱导人角质形成细胞（HaCaT）通过Akt/核因子-红细胞2相关（Nrf 2）途径合成还原型谷胱甘肽（GSH）的抗氧化酶中的作用，并阐明了其机制。岩藻黄素处理增加HaCaT细胞中GCLC和GSS的mRNA和蛋白水平。此外，岩藻黄素处理促进核转位和磷酸化的Nrf 2，一个转录因子的基因编码GCLC和GSS。染色质免疫沉淀和荧光素酶报告基因检测显示，岩藻黄素治疗增加了Nrf 2的抗氧化反应元件（ARE）序列和转录活性的Nrf 2的结合。岩藻黄质处理增加了Akt（活性形式）的磷酸化，Akt是Nrf 2的上调因子，暴露于LY 294002（磷酸肌醇3-激酶（PI 3 K）/Akt抑制剂）抑制了岩藻黄质诱导的Akt，Nrf 2的活化，导致GCLC和GSS表达降低。岩藻黄质对GCLC和GSS表达的影响与其对GSH水平的影响一致。此外，岩藻黄质处理恢复了紫外线B照射降低的GSH水平。总之，这些发现表明，岩藻黄质处理通过诱导Nrf 2驱动的参与GSH合成的酶的表达经由PI 3 K/Akt信号传导来增强细胞抗氧化防御。
Fucoxanthin, a natural carotenoid, is abundant in seaweed with antioxidant properties. This study investigated the role of fucoxanthin in the induction of antioxidant enzymes involved in the synthesis of reduced glutathione (GSH), synthesized by glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS), via Akt/nuclear factor-erythroid 2-related (Nrf2) pathway in human keratinocytes (HaCaT) and elucidated the underlying mechanism. Fucoxanthin treatment increased the mRNA and protein levels of GCLC and GSS in HaCaT cells. In addition, fucoxanthin treatment promoted the nuclear translocation and phosphorylation of Nrf2, a transcription factor for the genes encoding GCLC and GSS. Chromatin immune-precipitation and luciferase reporter gene assays revealed that fucoxanthin treatment increased the binding of Nrf2 to the antioxidant response element (ARE) sequence and transcriptional activity of Nrf2. Fucoxanthin treatment increased phosphorylation of Akt (active form), an up-regulator of Nrf2 and exposure to LY294002, a phosphoinositide 3-kinase (PI3K)/Akt inhibitor, suppressed the fucoxanthin-induced activation of Akt, Nrf2, resulting in decreased GCLC and GSS expression. In accordance with the effects on GCLC and GSS expression, fucoxanthin induced the level of GSH. In addition, fucoxanthin treatment recovered the level of GSH reduced by ultraviolet B irradiation. Taken together, these findings suggest that fucoxanthin treatment augments cellular antioxidant defense by inducing Nrf2-driven expression of enzymes involved in GSH synthesis via PI3K/Akt signaling.
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DOI：
10.1016/j.bbagen.2008.01.003
发表时间：
2008-04-01
影响因子：
3
作者：
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通讯作者：
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影响因子：
5.3
作者：
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影响因子：
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DOI：
10.1016/j.ijbiomac.2009.12.004
发表时间：
2010-03-01
影响因子：
8.2
作者：
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影响因子：
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