Document Detail

Roles of Ras-Erk in apoptosis of PC12 cells induced by trophic factor withdrawal or oxidative stress.
MedLine Citation:
PMID:  15784961     Owner:  NLM     Status:  MEDLINE    
To understand the role of Ras-MAPK (mitogen-activated protein kinase) in trophic factor withdrawal- and oxidative stress-induced apoptotic cell death processes, undifferentiated rat pheochromocytoma PC12 cells and a PC12 variant cell line stably expressing the Ras dominant-negative mutant (M-M17-26) were subjected to serum withdrawal in the absence or presence of H2O2 treatment. The extent of cell death was analyzed by lactate dehydrogenase release, internucleosomal DNA fragmentation, and caspase-3 assays. Both serum withdrawal and H2O2 treatment induced apoptotic cell death in PC12 cells, and the extent of cell death was greatly enhanced in M-M17-26 cells. DNA fragmentation induced by serum withdrawal or H2O2 treatment was blocked completely by a general caspase inhibitor, Z-VAD-FMK. A selective MAPK kinase inhibitor, U0126, blocked the H2O2-induced phosphorylation of Erk1/2 (extracellular signal-regulated kinase) in PC12 cells and increased the levels of active caspase-3 in M-M17-26 under serum withdrawal or H2O2 treatment. In addition, the short-term H2O2 treatment (5-30 min) was sufficient to cause DNA fragmentation in M-M17-26 cells even though H2O2 was removed and cells were incubated in regular growth medium with complete serum for 24 h. However, similar, short-term H2O2 treatment of PC12 cells did not induce DNA fragmentation 24 h later. These results suggest that the Ras-Erk pathway is critical in mediating protection against apoptotic cell death induced by either trophic factor withdrawal or increased oxidative stress.
Hao Jiang; Lijie Zhang; David Koubi; Jarret Kuo; Laurent Groc; Alba I Rodriguez; Tangella Jackson Hunter; Stephen Tang; Philip Lazarovici; Subhash C Gautam; Robert A Levine
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  25     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2005  
Date Detail:
Created Date:  2005-03-23     Completed Date:  2005-07-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-40     Citation Subset:  IM    
William T. Gossett Neurology Laboratories, Henry Ford Health System, Detroit, MI 48202. USA.
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MeSH Terms
Apoptosis / drug effects,  physiology*
Butadienes / pharmacology
Caspase 3
Caspases / metabolism
Culture Media, Serum-Free / pharmacology
Enzyme Inhibitors / pharmacology
Gene Expression
Genes, ras / genetics,  physiology*
Hydrogen Peroxide / pharmacology
MAP Kinase Kinase Kinases / antagonists & inhibitors,  metabolism
MAP Kinase Signaling System / drug effects,  physiology*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neurons / cytology*,  enzymology
Nitriles / pharmacology
Oxidants / pharmacology
Oxidative Stress / physiology*
PC12 Cells
Reg. No./Substance:
0/Butadienes; 0/Culture Media, Serum-Free; 0/Enzyme Inhibitors; 0/Nitriles; 0/Oxidants; 0/U 0126; 7722-84-1/Hydrogen Peroxide; EC Protein Kinase 1; EC Protein Kinase 3; EC Kinase Kinase Kinases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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

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