Document Detail


PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by up-regulating Bcl-2 expression.
MedLine Citation:
PMID:  16084648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neurotoxicity in primary neurons was induced using hypoxia/hypoglycemia (H/H), veratridine (10microM), staurosporine (1microM) or glutamate (100microM), which resulted in 72%, 67%, 75% and 66% neuronal injury, respectively. 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811; 10microM; Panacea Pharmaceuticals, Gaithersburg, MD) pretreatment for 24 h provided maximal neuroprotection of 89%, 42%, 47% and 89% against these toxicities, respectively. Glutamate or H/H treatment of cells increased cytosolic cytochrome c levels, which was blocked by pretreatment of cells with PAN-811. Pretreatment of neurons with PAN-811 produced a time-dependent increase in the protein level of Bcl-2, which was evident even after glutamate or H/H treatments. An up-regulation in the expression of the p53 and Bax genes was also observed following exposure to these neurotoxic insults; however, this increase was not suppressed by PAN-811 pretreatment. Functional inhibition of Bcl-2 by HA14-1 reduced the neuroprotective efficacy of PAN-811. PAN-811 treatment also abolished glutamate or H/H-mediated internucleosomal DNA fragmentation.
Authors:
R-W Chen; C Yao; X C M Lu; Z-G Jiang; R Whipple; Z Liao; H A Ghanbari; B Almassian; F C Tortella; J R Dave
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience     Volume:  135     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2005  
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-12-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-201     Citation Subset:  IM    
Affiliation:
Department of Applied Neurobiology, Division of Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA. renwu.chen@na.amedd.army.mil
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / pathology
Apoptosis / drug effects
Blotting, Western
Cell Survival / drug effects
Cells, Cultured
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Excitatory Amino Acid Antagonists / toxicity
Genes, bcl-2 / genetics*
Hypoglycemia / pathology
Neurons / drug effects*
Neuroprotective Agents / pharmacology*
Pyridines / pharmacology*
Rats
Rats, Sprague-Dawley
Staurosporine / antagonists & inhibitors,  toxicity
Thiosemicarbazones / pharmacology*
Up-Regulation / drug effects*
Veratridine / antagonists & inhibitors,  toxicity
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Neuroprotective Agents; 0/Pyridines; 0/Thiosemicarbazones; 143621-35-6/3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 62996-74-1/Staurosporine; 71-62-5/Veratridine; 9007-43-6/Cytochromes c

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


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