Document Detail


Iron contributes to the formation of catechol isoquinolines and oxidative toxicity induced by overdose dopamine in dopaminergic SH-SY5Y cells.
MedLine Citation:
PMID:  18500384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The selective loss of dopaminergic neurons in Parkinson's disease is suspected to correlate with the increase of cellular iron, which may be involved in the pathogenesis of PD by promotion of oxidative stress. This research investigated dopamine-induced oxidative stress toxicity contributed by iron and the production of dopamine-derived neurotoxins in dopaminergic SH-SY5Y cells. METHODS: After the SH-SY5Y cells were pre-incubated with dopamine and Fe2+ for 24 h, the cell viability, hydroxyl radical, melondialdehyde, cell apoptosis, and catechol isoquinolines were measured by lactate dehydrogenase assay, salicylic acid trapping method, thiobarbuteric acid assay, Hoechst 33258 staining and HPLC-electrochemical detection (HPLC-ECD), respectively. RESULTS: (1) Optimal dopamine (150 micromol/L) and Fe2+ (40 or 80 micromol/L) significantly increased the concentrations of hydroxy radicals and melondialdehyde in SH-SY5Y cells. (2) Induction with dopamine alone or dopamine and Fe2+ (dopamine/Fe2+) caused cell apoptosis. (3) Compared with untreated cells, the catechol isoquinolines, salsolinol and N-methyl-salsolinol in dopamine/Fe2+-induced cells were detected in increasing amounts. CONCLUSION: Due to dopamine/Fe2+-induced oxidative stress similar to the state in the parkinsonian substantia nigra neurons, dopamine and Fe2+ impaired SH-SY5Y cells could be used as the cell oxidative stress model of Parkinson's disease. The catechol isoquinolines detected in cells may be involved in the pathogenesis of Parkinson's disease as potential neurotoxins.
Authors:
Ran Wang; Hong Qing; Xiao-Qian Liu; Xiao-Lin Zheng; Yu-Lin Deng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience bulletin     Volume:  24     ISSN:  1673-7067     ISO Abbreviation:  -     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-26     Completed Date:  2008-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101256850     Medline TA:  Neurosci Bull     Country:  China    
Other Details:
Languages:  eng     Pagination:  125-32     Citation Subset:  IM    
Affiliation:
School of Life Science and Technology, Beijing Institute of Technology, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  physiology
Catechols / metabolism
Cell Line, Tumor
Cell Survival / drug effects,  physiology
Dopamine / toxicity*
Dose-Response Relationship, Drug
Humans
Hydroxyl Radical / metabolism
Iron / metabolism*
Iron Metabolism Disorders / complications,  metabolism,  physiopathology
Isoquinolines / metabolism*
Malondialdehyde / metabolism
Models, Biological
Nerve Degeneration / chemically induced,  metabolism*,  physiopathology
Neurons / drug effects,  metabolism*
Neurotoxins / toxicity
Oxidative Stress* / drug effects
Parkinson Disease / etiology,  metabolism,  physiopathology
Salsoline Alkaloids / metabolism
Up-Regulation / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Catechols; 0/Isoquinolines; 0/Neurotoxins; 0/Salsoline Alkaloids; 3352-57-6/Hydroxyl Radical; 525-72-4/salsolinol; 542-78-9/Malondialdehyde; 7439-89-6/Iron; 89-31-6/salsoline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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