Document Detail

Mechanisms of cell death in primary cortical neurons and PC12 cells.
MedLine Citation:
PMID:  11398190     Owner:  NLM     Status:  MEDLINE    
Increasing evidence suggests that the regulation of neuronal cell death is complex. In this study we compared the neurotoxic effects of tumor necrosis factor-alpha (TNFalpha), nitric oxide, and thrombin on primary rat cortical cell cultures and the neuronal PC12 cell line. Release of lactate dehydrogenase (LDH) and the intracellular accumulation of nucleosomes were used as indicators of necrosis and apoptosis, respectively. There was significant LDH release in both neuronal cell types, however, the pattern of LDH release was variable and agonist-dependent. In response to the nitric oxide generator, sodium nitroprusside (SNP), cortical cells exhibited pronounced LDH release and dramatic morphologic changes, whereas in differentiated PC12 cells, TNFalpha evoked release of LDH with no associated morphologic changes. Both neuronal cell types, but not undifferentiated PC12 cells, responded to TNFalpha and thrombin with increased apoptosis. Caspase inhibition, but not antioxidant treatment, reduced nucleosome accumulation in primary cortical cells, but not in differentiated PC12 cells. In the differentiated PC12 cells, caspase inhibition reduced TNFalpha-mediated LDH release, but not nucleosome accumulation. These data suggest mechanisms involved in neuronal cell death utilize multiple pathways that vary depending on the neurotoxic insult and are also influenced by subtle differences among neuronal cell phenotypes.
U Reimann-Philipp; R Ovase; P H Weigel; P Grammas
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  64     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-08     Completed Date:  2001-08-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  654-60     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
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MeSH Terms
Amino Acid Chloromethyl Ketones / pharmacology
Apoptosis / physiology*
Caspases / antagonists & inhibitors
Cells, Cultured
Cerebral Cortex / cytology*
Hemostatics / pharmacology
L-Lactate Dehydrogenase / metabolism
Neurons / cytology*,  enzymology
Neurotoxins / metabolism
Nitric Oxide / metabolism
Nitroprusside / pharmacology
Nucleosomes / metabolism
PC12 Cells
Protease Inhibitors / pharmacology
Thrombin / pharmacology
Tumor Necrosis Factor-alpha / pharmacology
Vasodilator Agents / pharmacology
Grant Support
R01 AG 15964-01/AG/NIA NIH HHS
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Hemostatics; 0/Neurotoxins; 0/Nucleosomes; 0/Protease Inhibitors; 0/Tumor Necrosis Factor-alpha; 0/Vasodilator Agents; 0/butyloxycarbonyl-aspartyl-fluoromethyl ketone; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; EC Dehydrogenase; EC; EC 3.4.22.-/Caspases

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