Abstract
The brain is particularly vulnerable to ischaemia; however, neurons can become tolerant to ischaemic insult. This tolerance has been shown to involve activation of NMDA receptors, but its mechanisms have not yet been fully elucidated. Using a preconditioning protocol, we show that neurons surviving to a transient NMDA exposure become resistant to the glutamatergic agonist. Using a proteomic approach, we found that alterations of the protein pattern of NMDA-resistant neurons are restricted mainly to the five collapsin response mediator proteins (CRMPs). A sustained increase in calpain activity following NMDA treatment is responsible for the production of cleaved CRMPs. Finally, we provide evidence for the involvement of the cleaved form of WT-CRMP2 in the down-regulation of NR2B. Our data suggests that, beside their role in neuronal morphogenesis, CRMPs may contribute to neuronal plasticity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biotin / metabolism
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Blotting, Western
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Calcium / metabolism
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Calpain / biosynthesis
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Calpain / physiology*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Down-Regulation / physiology
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Electrophoresis, Gel, Two-Dimensional
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Excitatory Amino Acid Agonists / pharmacology
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Glutamic Acid / toxicity
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Immunohistochemistry
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins / biosynthesis
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Mice
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N-Methylaspartate / pharmacology
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Nerve Tissue Proteins / genetics*
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Receptors, Cell Surface / metabolism*
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Recombinant Proteins / pharmacology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substances
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Excitatory Amino Acid Agonists
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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NR2B NMDA receptor
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Nerve Tissue Proteins
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Receptors, Cell Surface
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Receptors, N-Methyl-D-Aspartate
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Recombinant Proteins
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collapsin response mediator protein-2
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Glutamic Acid
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N-Methylaspartate
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Biotin
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Calpain
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Calcium