期刊
TOXICOLOGY
卷 278, 期 1, 页码 131-139出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2010.04.003
关键词
Ginseng; Glutamate cysteine ligase; Heme oxygenase-1; NF-E2-related factor 2; Red ginseng extract; Polychlorinated biphenyls; Reactive oxygen species
资金
- Korea Tobacco & Ginseng Corporation through the Korean Society of Ginseng Science
- Ministry of Education, Science and Technology, Republic of Korea [R0A-2004-000-10366-0]
- National Research Foundation of Korea [R0A-2004-000-10366-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that display a broad spectrum of biological and toxicological properties. There has been compelling evidence supporting that PCB-induced cytotoxicity is mediated through generation of reactive oxygen species (ROS). Considerable attention has been focused on identifying naturally occurring phytochemicals that are able to scavenge excess ROS, thereby protecting against oxidative cell death. Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. In this study, we have investigated the effect of red ginseng extract (RGE) on PCB126-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with PCB126 exhibited increased accumulation of intracellular ROS and underwent apoptosis as determined by positive in situ terminal end-labeling (TUNEL staining) and the perturbation of the mitochondrial membrane potential (Delta psi(m)). RGE treatment attenuated PCB126-induced cytotoxicity, apoptotic features and intracellular ROS accumulation. RGE treatment upregulated heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCLC) that are key antioxidant enzymes essential for cellular defense against oxidative stress. To elucidate the molecular mechanisms underlying RGE-mediated HO-1 and GCLC induction, we have examined the possible involvement of NF-E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, that plays an important role in the transcriptional regulation of diverse antioxidative genes via interaction with the antioxidant response element (ARE). Treatment of PC12 cells with RGE increased the nuclear translocation, ARE-binding and transcriptional activity of Nrf2 Moreover, U0126 and LY294002, pharmacological inhibitors of MEK1/2 and phosphatidylinositol 3-kinase which are upstream of ERK1/2 and Akt/protein kinase B, respectively attenuated HO-1 and GCLC expression as well as the ARE-driven transcriptional activation of Nrf2. These findings, taken together, suggest that HO-1 and GCLC induction via Nrf2 activation may contribute to cytoprotection exerted by RGE against PCB126-induced oxidative stress. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据