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標題: | Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells |
作者: | Chen, Pei-Yi Ho, Yi-Ru Wu, Ming-Jiuan Huang, Shun-Ping Chen, Po-Kong Tai, Mi-Hsueh Ho, Chi-Tang Yen, Jui-Hung |
貢獻者: | 生物科技系 |
關鍵字: | Natural flavonoid fisetin Cobalt chloride Improves bioavailability Inducible factor-1 Signaling pathway Erk activation Expression Hif-1 Transcription Brain |
日期: | 2015 |
上傳時間: | 2016-04-19 19:01:05 (UTC+8) |
出版者: | Royal Soc Chemistry |
摘要: | Fisetin (3,7,3', 4'-tetrahydroxyflavone), a flavonol compound of flavonoids, exhibits a broad spectrum of biological activities including anti-oxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The aim of this study is to investigate the cytoprotective effect of fisetin and the underlying molecular mechanism against hypoxia-induced cell death in PC12 cells. The results of this study showed that fisetin significantly restored the cell viability of PC12 cells under both cobalt chloride (CoCl2)-and low oxygen-induced hypoxic conditions. Treatment with fisetin successfully reduced the CoCl2-mediated reactive oxygen species (ROS) production, which was accompanied by an increase in the cell viability of PC12 cells. Furthermore, we found that treatment of PC12 cells with fisetin markedly upregulated hypoxia-inducible factor 1 alpha (HIF-1 alpha), its nuclear accumulation and the hypoxia-response element (HRE)-driven transcriptional activation. The fisetin-mediated cytoprotection during CoCl2 exposure was significantly attenuated through the administration of HIF-1 alpha siRNA. Moreover, we demonstrated that MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK and phosphatidylinositol 3-kinase (PI3 K) inhibitors significantly blocked the increase in cell survival that was induced by fisetin treatment under hypoxic conditions. Consistently, increased phosphorylation of ERK, p38 and Akt proteins was observed in PC12 cells treated with fisetin. However, the fisetin-induced HRE-driven transcription was not affected by inhibition of these kinase signaling pathways. Current results reveal for the first time that fisetin promotes cell survival and protects against hypoxia-induced cell death through ROS scavenging and the activation of HIF1 alpha-, MAPK/ERK-,p38 MAPK- and PI3 K/Akt-dependent signaling pathways in PC12 cells. |
關聯: | Food & Function, v.6 n.1, pp.287-296 |
顯示於類別: | [生物科技系(所)] 期刊論文
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