Document Detail


MPTP-induced reactive oxygen species promote cell death through a gradual activation of caspase-3 without expression of GRP78/Bip as a preventive measure against ER stress in PC12 cells.
MedLine Citation:
PMID:  12770613     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucose-regulated protein 78 (GRP78)/Immunoglobulin binding protein (Bip) is a chaperone which functions to protect cells from endoplasmic reticulum (ER) stress. GRP78/Bip is expressed following ER stress induced by thapsigargin, tunicamycin or chemical factors. However, the mechanism of progression of ER stress against stress factors is still obscure. We examined whether reactive oxygen species (ROS) were involved in GRP78/Bip expression and caspase-3 activity was induced in PC12 cells using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce ROS. We report that PC12 cells lost viability in the presence of MPTP for 24 hours as a partial effect of ROS. We also show that N-acetyl-L-cysteine diminished the MPTP-induced apoptosis with expunction of ROS. Furthermore, we observed that GRP78/Bip was not up-regulated and the caspase-3 activity was increased in the presence of MPTP. These results suggest that insubstantial ROS do not contribute to the ER stress-mediated cell death while caspase-3 is involved in ROS-promoted cell death in MPTP-treated cells.
Authors:
Koji Shimoke; Motoshige Kudo; Toshihiko Ikeuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  73     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-28     Completed Date:  2003-06-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  581-93     Citation Subset:  IM    
Affiliation:
Laboratory of Neurobiology, Faculty of Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan. shimoke@ipcku.kansai-u.ac/jp
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
Animals
Carrier Proteins / biosynthesis*
Caspase 3
Caspases / biosynthesis*
Cell Survival / drug effects
Endoplasmic Reticulum / enzymology,  metabolism*
Enzyme Activation / drug effects
Heat-Shock Proteins*
Lipid Peroxidation / drug effects
Lipid Peroxides / analysis
Molecular Chaperones / biosynthesis*
Oxidative Stress / drug effects*
PC12 Cells
Rats
Reactive Oxygen Species / metabolism*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Heat-Shock Proteins; 0/Lipid Peroxides; 0/Molecular Chaperones; 0/Reactive Oxygen Species; 0/molecular chaperone GRP78; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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