Subtoxic concentration of manganese synergistically potentiates 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells
文献类型:期刊论文
作者 | Wang, RG; Zhu, XZ |
刊名 | BRAIN RESEARCH
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出版日期 | 2003-01-24 |
卷号 | 961期号:1页码:131-138 |
关键词 | Parkinson's disease 1-methyl-4-phenylpyridinium manganese reactive oxygen species neurotoxicity PC12 cell |
ISSN号 | 0006-8993 |
DOI | 10.1016/S0006-8993(02)03886-6 |
文献子类 | Article |
英文摘要 | Endogenous or exogenous substances that are toxic to dopaminergic cells have been proposed as possible cause of idiopathic Parkinson's disease (PD). 1-Methyl-4-phenylpyridinium (MPP+) and manganese are dopaminergic neurotoxins causing a parkinsonism-like syndrome. Here, we studied the possible synergistic reaction between these two neurotoxins using rat PC12 pheochromocytoma cells. MPP+ induced a delayed neurotoxicity in PC12 cells. Although low concentration of manganese did not cause cell damage, it markedly enhanced MPP+-induced neurotoxicity with characteristics of apoptosis, such as DNA laddering and activation of caspase-3. To understand the mechanism of enhancement of subtoxic concentration of manganese on MPP+-induced neurotoxicity, we investigated the reactive oxygen species (ROS) generation using a molecular probe, 2',7'-dichlorofluorescein diacetate. Although subtoxic concentration of manganese alone did not induce ROS increase, it significantly enhanced the ROS generation induced by MPP+. We also determined the intracellular MPP, content. A time- and concentration-dependent increase of MPP+ levels was found in PC12 cells treated with MPP+. The accumulation of MPP+ by PC12 cells was not affected by manganese. Taken together, these studies suggest that co-treatment with MPP+ and manganese may induce synergistic neurotoxicity in PC12 cells and that subtoxic concentration of manganese may potentiate the effect of MPP+ by an ROS-dependent pathway. (C) 2002 Elsevier Science B.V. All rights reserved. |
WOS关键词 | MITOCHONDRIAL COMPLEX-I ; PARKINSONS-DISEASE ; DOPAMINE DEPLETION ; INDUCED APOPTOSIS ; COMBINED PARAQUAT ; OXIDATIVE STRESS ; MPTP ; NEURONS ; MECHANISM ; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE |
WOS研究方向 | Neurosciences & Neurology |
语种 | 英语 |
WOS记录号 | WOS:000180756600018 |
出版者 | ELSEVIER SCIENCE BV |
源URL | [http://119.78.100.183/handle/2S10ELR8/274271] ![]() |
专题 | 药理学第二研究室 |
通讯作者 | Zhu, XZ |
作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 200031, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, RG,Zhu, XZ. Subtoxic concentration of manganese synergistically potentiates 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells[J]. BRAIN RESEARCH,2003,961(1):131-138. |
APA | Wang, RG,&Zhu, XZ.(2003).Subtoxic concentration of manganese synergistically potentiates 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells.BRAIN RESEARCH,961(1),131-138. |
MLA | Wang, RG,et al."Subtoxic concentration of manganese synergistically potentiates 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells".BRAIN RESEARCH 961.1(2003):131-138. |
入库方式: OAI收割
来源:上海药物研究所
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