Document Detail


Kainic acid-induced neuronal cell death in cerebellar granule cells is not prevented by caspase inhibitors.
MedLine Citation:
PMID:  11877339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. We examined the role of non-NMDA receptors in kainic acid (KA)-induced apoptosis in cultures of rat cerebellar granule cells (CGCs). KA (1 - 500 microM) induced cell death in a concentration-dependent manner, which was prevented by NBQX and GYKI 52466, non-NMDA receptor antagonists. Moreover, AMPA blocked KA-induced excitotoxicity, through desensitization of AMPA receptors. 2. Similarly, KA raised the intracellular calcium concentration of CGCs, which was inhibited by NBQX and GYKI 52466. Again, AMPA (100 microM) abolished the KA (100 microM)-induced increase in intracellular calcium concentration. 3. KA-induced cell death in CGCs had apoptotic features, which were determined morphologically, by DNA fragmentation, and by expression of the prostate apoptosis response-4 protein (Par-4). 5. KA (500 microM) slightly (18%) increased caspase-3 activity, which was strongly enhanced by colchicine (1 microM), an apoptotic stimulus. However, neither Z-VAD.fmk, a pan-caspase inhibitor, nor the more specific caspase-3 inhibitor, Ac-DEVD-CHO, prevented KA-induced cell death or apoptosis. In contrast, both drugs inhibited colchicine-induced apoptosis. 5. The calpain inhibitor ALLN had no effect on KA or colchicine-induced neurotoxicity. 6. Our findings indicate that colchicine-induced apoptosis in CGCs is mediated by caspase-3 activation, unlike KA-induced apoptosis.
Authors:
Ester Verdaguer; Elvira García-Jordà; Andrés Jiménez; Alessandra Stranges; Francesc X Sureda; Anna M Canudas; Elena Escubedo; Jordi Camarasa; Mercè Pallàs; Antoni Camins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  135     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-05     Completed Date:  2002-08-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1297-307     Citation Subset:  IM    
Affiliation:
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Apoptosis Regulatory Proteins
Carrier Proteins / metabolism
Caspase 3
Caspases / antagonists & inhibitors*
Cell Survival / drug effects
Cells, Cultured
Cerebellum / cytology,  drug effects*,  metabolism
Cysteine Proteinase Inhibitors / pharmacology
Enzyme Precursors / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins*
Kainic Acid / toxicity*
Neurons / drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Receptors, AMPA / metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Carrier Proteins; 0/Cysteine Proteinase Inhibitors; 0/Enzyme Precursors; 0/Intracellular Signaling Peptides and Proteins; 0/Receptors, AMPA; 0/prostate apoptosis response-4 protein; 487-79-6/Kainic Acid; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases
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