Rotenone-induced neurotoxicity of THP-1 cells requires production of reactive oxygen species and activation of phosphatidylinositol 3-kinase
文献类型:期刊论文
作者 | Hu, Jing-Hui; Zhu, Xing-Zu |
刊名 | BRAIN RESEARCH
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出版日期 | 2007-06-11 |
卷号 | 1153页码:12-19 |
关键词 | rotenone inflammation THP-1 cells phosphatidylinositol 3-kinase Akt reactive oxygen species |
ISSN号 | 0006-8993 |
DOI | 10.1016/j.brainres.2007.03.006 |
文献子类 | Article |
英文摘要 | Parkinson's disease is characterized by slow and progressive degeneration of dopaminergic neurons. Increasing evidence has suggested an important role for exposure to pesticides such as rotenone in the pathogenesis of Parkinson's disease. Although rotenone can elicit immune responses in microglia, the intracellular signaling events mediating these effects are poorly defined. Here we show that cell-free supernatants of rotenone-treated monocytic THP-1 cells induced cytotoxicity in dopaminergic neuroblastoma SH-SY5Y cells. Exposure of THP-1 cells to rotenone led to transient production of reactive oxygen species (ROS) and phosphorylation of Akt. Akt activation was also induced by exogenous hydrogen peroxide. Pretreatment of THP-1 cells with either a phosphatidylinositol 3-kinase (PI3K) inhibitor or ROS scavengers prevented Akt activation and protected SH-SY5Y cells from the cytotoxic effect of conditioned media from rotenone-treated THP-1 cells. Roterione treatment of THP-1 cells also led to upregulation of cyclooxygenase-2 and secretion of prostaglandin E-2. These results suggest that rotenone-induced activation of ROS/PI3K/Akt pathway in THP-1 cells leads to the release of factors that are toxic to SH-SY5Y cells and have implications for the onset of Parkinson's disease. (c) 2007 Elsevier B.V. All rights reserved. |
WOS关键词 | NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; PARKINSONS-DISEASE ; DOPAMINERGIC-NEURONS ; MICROGLIAL ACTIVATION ; SIGNAL-TRANSDUCTION ; PROTEIN-KINASES ; EXPRESSION ; PTEN ; DEGENERATION ; APOPTOSIS |
WOS研究方向 | Neurosciences & Neurology |
语种 | 英语 |
WOS记录号 | WOS:000247423800002 |
出版者 | ELSEVIER SCIENCE BV |
源URL | [http://119.78.100.183/handle/2S10ELR8/273227] ![]() |
专题 | 药理学第二研究室 |
通讯作者 | Hu, Jing-Hui |
作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Hu, Jing-Hui,Zhu, Xing-Zu. Rotenone-induced neurotoxicity of THP-1 cells requires production of reactive oxygen species and activation of phosphatidylinositol 3-kinase[J]. BRAIN RESEARCH,2007,1153:12-19. |
APA | Hu, Jing-Hui,&Zhu, Xing-Zu.(2007).Rotenone-induced neurotoxicity of THP-1 cells requires production of reactive oxygen species and activation of phosphatidylinositol 3-kinase.BRAIN RESEARCH,1153,12-19. |
MLA | Hu, Jing-Hui,et al."Rotenone-induced neurotoxicity of THP-1 cells requires production of reactive oxygen species and activation of phosphatidylinositol 3-kinase".BRAIN RESEARCH 1153(2007):12-19. |
入库方式: OAI收割
来源:上海药物研究所
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