The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress

被引：127

作者：

Hwang, Yong Pil ^{[1
]}

Jeong, Hye Gwang ^{[1
]}

机构：

[1] Chosun Univ, Coll Pharm, Res Ctr Proteineous Mat, Dept Pharm, Kwangju 501759, South Korea

来源：

FEBS LETTERS | 2008年 / 582卷 / 17期

关键词：

kahweol; heme oxygenase-1; NF-E2 related factor 2; phosphatidylinositol; 3-kinase; p38; kinase; neuroprotection;

D O I：

10.1016/j.febslet.2008.06.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, we investigated the mechanisms of kahweol protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with kahweol significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Kahweol also up-regulated heme oxygenase-1 (HO-1) expression, which conferred neuroprotection against 6-OHDA-induced oxidative injury. Moreover, kahweol induced PI3K and p38 activation, which are involved in the induction of Nrf2, HO-1 expression, and neuroprotection. These results suggest that regulation of the anti-oxidant enzyme HO-1 via the PI3K and p38/Nrf2 signaling pathways controls the intracellular levels of ROS. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：2655 / 2662

页数：8

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