Document Detail


Effect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells.
MedLine Citation:
PMID:  14514037     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Agmatine is an endogenous guanido amine and has been shown to be neuroprotective in vitro and in vivo. The aims of this study are to investigate whether agmatine is protective against cell death induced by different agents in cultured neurons and PC12 cells.
METHODS: Cell death in neurons, cultured from neonatal rat cortex, was induced by incubating with (a) NMDA (100 microM) for 10 min, (b) staurosporine (protein kinase inhibitor, 100 nM) for 24 h, and (c) calcimycin (calcium ionophore, 100 nM) for 24 h in the presence and absence of agmatine (1 micro M to 1 mM). Cell death in PC12 cells was induced by exposure to glutamate (10 mM), staurosporine (100 nM), and calcimycin (100 nM). The activity of lactate dehydrogenase (LDH) in the medium was measured as the marker of cell death and normalized to cellular LDH activity.
RESULTS: Agmatine significantly reduced the medium LDH in NMDA-treated neurons but failed to reduce the release of LDH induced by staurosporin or calcimycin. In PC12 cells, agmatine significantly reduced LDH release induced by glutamate exposure, but not by staurosporine or calcimycin. Agmatine itself neither increased LDH release nor directly inhibited the enzyme activity.
CONCLUSION: We conclude that agmatine protects against NMDA excitotoxicity in neurons and PC12 cells but not the cell death induced by protein kinase blockade or increase in cellular calcium.
Authors:
Meng-Yang Zhu; John E Piletz; Angelos Halaris; Soundar Regunathan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular and molecular neurobiology     Volume:  23     ISSN:  0272-4340     ISO Abbreviation:  Cell. Mol. Neurobiol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-29     Completed Date:  2004-04-30     Revised Date:  2014-02-03    
Medline Journal Info:
Nlm Unique ID:  8200709     Medline TA:  Cell Mol Neurobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  865-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Agmatine / pharmacology*
Animals
Calcimycin / pharmacology
Cell Death / drug effects,  physiology
Cerebral Cortex / drug effects,  metabolism,  pathology
Enzyme Inhibitors / pharmacology
Fetus
Glutamic Acid / metabolism,  pharmacology
Ionophores / pharmacology
L-Lactate Dehydrogenase / metabolism
N-Methylaspartate / antagonists & inhibitors,  pharmacology
Nerve Degeneration / chemically induced,  physiopathology,  prevention & control*
Neurons / drug effects*,  metabolism,  pathology
Neuroprotective Agents / pharmacology*
Neurotoxins / antagonists & inhibitors*
PC12 Cells
Protein Kinase Inhibitors
Protein Kinases / metabolism
Rats
Staurosporine / pharmacology
Grant Support
ID/Acronym/Agency:
MS 57601//PHS HHS; NS 39445/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Ionophores; 0/Neuroprotective Agents; 0/Neurotoxins; 0/Protein Kinase Inhibitors; 37H9VM9WZL/Calcimycin; 3KX376GY7L/Glutamic Acid; 6384-92-5/N-Methylaspartate; 70J407ZL5Q/Agmatine; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.-/Protein Kinases; H88EPA0A3N/Staurosporine

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


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