Document Detail

Distinct mechanisms account for beta-amyloid toxicity in PC12 and differentiated PC12 neuronal cells.
MedLine Citation:
PMID:  12824697     Owner:  NLM     Status:  MEDLINE    
Whether reactive oxygen species (ROS) mediate beta-amyloid (A beta) neurotoxicity remains controversial. Naive PC12 cells (PC12) and nerve growth factor-differentiated PC12 cells (dPC12) were used to study the role of ROS in cell death induced by A beta(25-35). The viability of PC12 and dPC12 cells decreased by 30-40% after a 48-hour exposure to 20 microM A beta(25-35). Microscopic examination showed that A beta(25-35) induced necrosis in PC12 cells and apoptosis in dPC12 cells. Vitamin E (100 microM) and other antioxidants protected PC12 cells, but not dPC12 cells, against the cytotoxic effect of A beta(25-35). Since H(2)O(2) has been proposed to be involved in A beta toxicity, the effects of H(2)O(2) on PC12 and dPC12 cells were studied. Differentiated PC12 cells appeared to be significantly more resistant to H(2)O(2) than naive PC12 cells. These data suggest that ROS may mediate A beta(25-35) toxicity in PC12 cells but not in dPC12 cells. Because the intracellular levels of ROS were elevated during the differentiation of PC12 cells, the baseline levels of ROS in these two model cell types may determine the intracellular mediators for A beta(25-35) toxicity. Therefore, the protective effects of antioxidants against A beta may depend upon the redox state of the cells.
Yen-Jen Sung; Chia-lo Cheng; Chaio-Sung Chen; Hsien-Bin Huang; Fong-Lee Huang; Pei-Chun Wu; Ming-Shi Shiao; Huey-Jen Tsay
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical science     Volume:  10     ISSN:  1021-7770     ISO Abbreviation:  J. Biomed. Sci.     Publication Date:    2003 Jul-Aug
Date Detail:
Created Date:  2003-06-25     Completed Date:  2004-03-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421567     Medline TA:  J Biomed Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  379-88     Citation Subset:  IM    
Copyright Information:
Copyright 2003 National Science Council, ROC and S. Karger AG, Basel
Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
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MeSH Terms
Amyloid beta-Protein / antagonists & inhibitors,  toxicity*
Antioxidants / pharmacology
Caspases / metabolism
Cell Differentiation / drug effects
Cell Survival / drug effects
DNA Fragmentation / drug effects*
Nerve Growth Factor / pharmacology
Neurons / cytology,  physiology*
Oxidative Stress
PC12 Cells
Peptide Fragments
Reactive Oxygen Species / metabolism*
Vitamin E / pharmacology
Reg. No./Substance:
0/Amyloid; 0/Amyloid beta-Protein; 0/Antioxidants; 0/Peptide Fragments; 0/Reactive Oxygen Species; 0/amyloid beta-protein (25-36); 1406-18-4/Vitamin E; 9061-61-4/Nerve Growth Factor; EC 3.4.22.-/Caspases

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