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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
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
通讯作者Zhu, xz()
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
WOS类目Neurosciences
语种英语
WOS记录号WOS:000180756600018
出版者ELSEVIER SCIENCE BV
URI标识http://www.irgrid.ac.cn/handle/1471x/2376142
专题武汉病毒研究所
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
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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.

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来源:武汉病毒研究所

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