| Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis. | |
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MedLine Citation:
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PMID: 15950951 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal alterations are involved in several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We studied the possible pathways involved in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation, selective caspase inhibitors did not attenuate apoptosis. Inhibitors of other cysteine proteases such as PD150606 (a calpain-specific inhibitor), Z-Phe-Ala fluoromethyl ketone (a cathepsins-inhibitors) and N(alpha)-p-tosyl-l-lysine chloromethyl ketone (serine-proteases inhibitor) also had no effect on cell death/apoptosis induced by colchicine. However, BAPTA-AM 10 microM (intracellular calcium chelator) prevented apoptosis mediated by cytoskeletal alteration. These data indicate that calcium modulates colchicine-induced apoptosis in CGNs. PARP-1 inhibitors did not prevent apoptosis mediated by colchicine. Finally, colchicine-induced apoptosis in CGNs was attenuated by kenpaullone, a cdk5 inhibitor. Kenpaullone and indirubin also prevented cdk5/p25 activation mediated by colchicine. These findings indicate that cytoskeletal alteration can compromise cdk5 activation, regulating p25 formation and suggest that cdk5 inhibitors attenuate apoptosis mediated by cytoskeletal alteration. The present data indicate the potential therapeutic value of drugs that prevent the formation of p25 for the treatment of neurodegenerative disorders. |
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Authors:
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Elvira G Jordà; Ester Verdaguer; Andrés Jimenez; S Garcia de Arriba; Clemens Allgaier; Mercè Pallàs; Antoni Camins |
Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 70 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-04 Completed Date: 2005-08-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 470-80 Citation Subset: IM |
Affiliation:
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Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology* Cell Survival / drug effects, physiology Cells, Cultured Cerebellum / cytology, drug effects Colchicine / pharmacology Cytoskeleton / drug effects, physiology* Dose-Response Relationship, Drug Egtazic Acid / analogs & derivatives*, pharmacology Neurons / cytology*, drug effects, physiology* Rats Rats, Sprague-Dawley Signal Transduction / drug effects, physiology* |
| Chemical | |
Reg. No./Substance:
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64-86-8/Colchicine; 67-42-5/Egtazic Acid; 85233-19-8/1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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