Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/23144
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    標題: Regulation of Heme Oxygenase-1 Expression and MAPK Pathways in Response to Kaempferol and Rhamnocitrin in PC12 Cells
    作者: Jing-Ting Hong
    Jui-Hung Yen
    Lisu Wang
    Ya-Hsuan Lo
    Zong-Tsi Chen
    Ming-Jiuan Wu
    貢獻者: 生物科技系
    食品科技系
    醫藥化學系
    關鍵字: Kaempferol
    Rhamnocitrin
    PC12 cells
    HO-1
    MAPK pathway
    日期: 2009-05
    上傳時間: 2010-10-27 14:14:35 (UTC+8)
    摘要: Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially neural diseases. Our aim of research is to investigate the protective effects and mechanisms of kaempferol and rhamnocitrin (kaempferol-7-methyl ether) on oxidative damage in rat pheochromocytoma PC12 cells induced by a limited supply of serum and hydrogen peroxide (H2O2). The current result demonstrated that kaempferol protected PC12 cells from serum deprivation-induced apoptosis. Pretreatment of cells with kaempferol also diminished intracellular generation of reactive oxygen species (ROS) in response to H2O2 and strongly elevated cell viability. RT-Q-PCR and Western blotting revealed that kaempferol and rhamnocitrin significantly induced heme oxygenase (HO)-1 gene expression. Addition of zinc protoporphyrin (Znpp), a HO-1 competitive inhibitor, significantly attenuated their protective effects in
    H2O2-treated cells, indicating the vital role of HO-1 in cell resistance to oxidative injury. While investigating the signaling pathways responsible for HO-1 induction, we observed that kaempferol induced sustained extracellular signal-regulated protein kinase 1/2 (ERK1/2) in PC12 cells grown in low serum medium; while rhamnocitrin only stimulated transient ERK cascade. Addition of U0126, a highly selective inhibitor of MEK1/ 2, which is upstream of ERK1/2, had no effect on kaempferol- or rhamnocitrin-induced HO-1 mRNA expression, indicating no direct cross-talk between these two pathways. Furthermore, both kaempferol and rhamnocitrin were able to persistently attenuate p38 phosphorylation. Taking together, the above findings suggest that kaempferol and rhamnocitrin can augment cellular antioxidant defense capacity, at least in part, through regulation of HO-1 expression and MAPK signal transduction.
    關聯: Toxicology and Applied Pharmacology 237(1):p.59-68
    显示于类别:[生物科技系(所)] 期刊論文

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