Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52080
標題: 藻褐素可經由溫和促氧化作用而活化Nrf2/ARE系統促進HO-1及NQO1之表現
Fucoxanthin enhances HO-1 and NQO1 expression partly through activation of the Nrf2/ARE system by moderate pro-oxidative actions
作者: Chiu, Yu-Ting
邱郁婷
關鍵字: fucoxanthin
藻褐素
Nrf2
ARE
HO-1
NQO1
pro-oxidative actions
Nrf2
ARE
HO-1
NQO1
促氧化作用
出版社: 食品暨應用生物科技學系所
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摘要: 藻褐素(Fucoxanthin)是富含於褐藻中的類胡蘿蔔素,具有抗氧化的活性,但因帶有5, 6-monoepoxide不穩定的結構,而易受到親核性分子的攻擊,導致促氧化的現象。本研究的目的為探討藻褐素是否藉由促氧化現象而啟動Nuclear transcription factor erythoid 2p45 (NF-E2)-related factor 2 (Nrf2) / antioxidant-response element (ARE)路徑來活化生物轉換/抗氧化酵素的表現。我們用不同濃度(0.5-20 μM)的藻褐素處理小鼠胚胎肝細胞株(BNL CL.2) 0-24小時。結果顯示:以藻褐素處理6小時後,細胞內reactive oxygen species (ROS)含量顯著增加,而加入α-d-tocopherol (30 μM)預培養則會顯著降低,說明藻褐素有促氧化的作用。以藻褐素培養細胞12小時之後,顯著促進phospho-ERK和phospho-p38的表現;同時,核內Nrf2蛋白質表現也顯著增加2.5倍。此外,以藻褐素培養12小時之後,會明顯促進核內Nrf2與啟動子上ARE序列結合,並且顯著促進HO-1 (Heme oxygenase-1)和NQO1 (NAD(P)H:quinone oxidoreductase 1)蛋白質與mRNA的表現。以上各項結果皆以5 μM藻褐素的作用最強。最後以Nrf2 siRNA技術確定作用路徑,結果發現以藻褐素(5 μM) + Nrf2 siRNA (70 nM)處理後細胞核內Nrf2、HO-1及NQO1的蛋白表現大幅降低。本研究的結果顯示:藻褐素確實可藉由ERK和p38 MAPK訊號傳遞路徑活化Nrf2/ARE系統,調節下游HO-1及NQO1的蛋白表現,作用機制與促氧化作用有關。
Fucoxanthin is the major carotenoid in brown sea algae and has been shown to exert antioxidant activity. However, Fucoxanthin is highly unstable and it may attack by nucleophile molecule to cause the pro-oxidative actions because of its unique chemical structure including 5, 6-monoepoxide. Thus, the purpose of this research was to determine whether fucoxanthin activates cellular antioxidant enzyme expression via up-regulation of Nrf2/ antioxidant-response element (ARE) mechanism through its pro-oxidative actions. We incubated mouse hepatic BNL CL.2 cells with fucoxanthin (0.5-20 μM) for 0-24 h. We found that fucoxanthin significantly increased cellular reactive oxygen species level for 6 h and that inclusion of α-d-tocopherol (30 μM) significantly attenuated the increase of ROS, indicating that fucoxanthin has pro-oxidative actions. In addition, fucoxanthin significantly increased phosphorylation of ERK and p38 and markedly increased the protein expression (2.5 fold) of nuclear Nrf2 after incubation for 12 h. Moreover, fucoxanthin significantly enhanced the binding activities between nuclear Nrf2 and ARE, increased protein expression of HO-1 and NQO1 after incubation for 12 h. The use of small interfering RNA inhibition of Nrf2 leads to decreased HO-1and NQO1 protein expression. Thus, the present study demonstrates that fucoxanthin can activate the MAPK signaling pathway and the Nrf2/ARE system to induce HO-1 and NQO1gene expression, possibly through its pro-oxidative actions.
URI: http://hdl.handle.net/11455/52080
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