RGD Reference Report - Knockdown of m-calpain increases survival of primary hippocampal neurons following NMDA excitotoxicity. - Rat Genome Database

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Knockdown of m-calpain increases survival of primary hippocampal neurons following NMDA excitotoxicity.

Authors: Bevers, Matthew B  Lawrence, Eric  Maronski, Margaret  Starr, Neasa  Amesquita, Michael  Neumar, Robert W 
Citation: Bevers MB, etal., J Neurochem. 2009 Mar;108(5):1237-50. doi: 10.1111/j.1471-4159.2008.05860.x. Epub 2009 Jan 22.
RGD ID: 13792555
Pubmed: PMID:19141074   (View Abstract at PubMed)
PMCID: PMC2676331   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1471-4159.2008.05860.x   (Journal Full-text)

The calpain family of cysteine proteases has a well-established causal role in neuronal cell death following acute brain injury. However, the relative contribution of calpain isoforms to the various forms of injury has not been determined as available calpain inhibitors are not isoform-specific. In this study, we evaluated the relative role of m-calpain and mu-calpain in a primary hippocampal neuron model of NMDA-mediated excitotoxicity. Baseline mRNA expression for the catalytic subunit of m-calpain (capn2 ) was found to be 50-fold higher than for the mu-calpain catalytic subunit (capn1) based on quantitative real-time PCR. Adeno-associated viral vectors designed to deliver short hairpin RNAs targeting capn1 or capn2 resulted in 60% and 90% knockdown of message respectively. Knockdown of capn2 but not capn1 increased neuronal survival after NMDA exposure at 21 days in vitro. Nuclear translocation of calpain substrates apoptosis inducing factor, p35/p25 and collapsin response mediator protein (CRMP) 2-4 was not detected after NMDA exposure in this model. However, nuclear translocation of CRMP-1 was observed and was prevented by capn2 knockdown. These findings provide insight into potential mechanisms of calpain-mediated neurodegeneration and have important implications for the development of isoform-specific calpain inhibitor therapy.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
N-methyl-D-aspartic acid increases activityISOCapn2 (Rattus norvegicus)13792555; 13792555NMDA increases activity of Capn2 in rat hippocampal neuron culturesRGD 
N-methyl-D-aspartic acid increases activityEXP 13792555NMDA increases activity of Capn2 in rat hippocampal neuron culturesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Capn2  (calpain 2)

Genes (Mus musculus)
Capn2  (calpain 2)

Genes (Homo sapiens)
CAPN2  (calpain 2)

Objects referenced in this article
Gene Crmp1 collapsin response mediator protein 1 Rattus norvegicus

Additional Information