| Activation of calpain I converts excitotoxic neuron death into a caspase-independent cell death. | |
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MedLine Citation:
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PMID: 10828077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glutamate receptor overactivation contributes to neuron death after stroke, trauma, and epileptic seizures. Exposure of cultured rat hippocampal neurons to the selective glutamate receptor agonist N-methyl-d-aspartate (300 microm, 5 min) or to the apoptosis-inducing protein kinase inhibitor staurosporine (300 nm) induced a delayed neuron death. In both cases, neuron death was preceded by the mitochondrial release of the pro-apoptotic factor cytochrome c. Unlike staurosporine, the N-methyl-d-aspartate-induced release of cytochrome c did not lead to significant activation of caspase-3, the main caspase involved in the execution of neuronal apoptosis. In contrast, activation of the Ca(2+)-activated neutral protease calpain I was readily detectable after the exposure to N-methyl-d-aspartate. In a neuronal cell-free apoptosis system, calpain I prevented the ability of cytochrome c to activate the caspase cascade by inhibiting the processing of procaspase-3 and -9 into their active subunits. In the hippocampal neuron cultures, the inhibition of calpain activity restored caspase-3-like protease activity after an exposure to N-methyl-d-aspartate. Our data demonstrate the existence of signal transduction pathways that prevent the entry of cells into a caspase-dependent cell death program after the mitochondrial release of cytochrome c. |
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Authors:
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S Lankiewicz; C Marc Luetjens; N Truc Bui; A J Krohn; M Poppe; G M Cole; T C Saido; J H Prehn |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 275 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-07-11 Completed Date: 2000-07-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 17064-71 Citation Subset: IM |
Affiliation:
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Interdisciplinary Center for Clinical Research (IZKF), Research Group "Apoptosis and Cell Death," Westphalian Wilhelms University, D-48149 Münster, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Calpain / metabolism* Caspases / metabolism Cells, Cultured Cytochrome c Group / metabolism Enzyme Activation Hippocampus / drug effects, enzymology Microscopy, Fluorescence Mitochondria / drug effects, enzymology N-Methylaspartate / pharmacology* Neurons / cytology, drug effects*, enzymology Rats |
| Chemical | |
Reg. No./Substance:
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0/Cytochrome c Group; 6384-92-5/N-Methylaspartate; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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