RGD Reference Report - Calpastatin is up-regulated in response to hypoxia and is a suicide substrate to calpain after neonatal cerebral hypoxia-ischemia. - Rat Genome Database

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Calpastatin is up-regulated in response to hypoxia and is a suicide substrate to calpain after neonatal cerebral hypoxia-ischemia.

Authors: Blomgren, K  Hallin, U  Andersson, AL  Puka-Sundvall, M  Bahr, BA  McRae, A  Saido, TC  Kawashima, S  Hagberg, H 
Citation: Blomgren K, etal., J Biol Chem. 1999 May 14;274(20):14046-52.
RGD ID: 5683321
Pubmed: PMID:10318818   (View Abstract at PubMed)

In a model of cerebral hypoxia-ischemia in the immature rat, widespread brain injury is produced in the ipsilateral hemisphere, whereas the contralateral hemisphere is left undamaged. Previously, we found that calpains were equally translocated to cellular membranes (a prerequisite for protease activation) in the ipsilateral and contralateral hemispheres. However, activation, as judged by degradation of fodrin, occurred only in the ipsilateral hemisphere. In this study we demonstrate that calpastatin, the specific, endogenous inhibitor protein to calpain, is up-regulated in response to hypoxia and may be responsible for the halted calpain activation in the contralateral hemisphere. Concomitantly, extensive degradation of calpastatin occurred in the ipsilateral hemisphere, as demonstrated by the appearance of a membrane-bound 50-kDa calpastatin breakdown product. The calpastatin breakdown product accumulated in the synaptosomal fraction, displaying a peak 24 h post-insult, but was not detectable in the cytosolic fraction. The degradation of calpastatin was blocked by administration of CX295, a calpain inhibitor, indicating that calpastatin acts as a suicide substrate to calpain during hypoxia-ischemia. In summary, calpastatin was up-regulated in areas that remain undamaged and degraded in areas where excessive activation of calpains and infarction occurs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Brain Hypoxia-Ischemia  ISOCast (Rattus norvegicus)5683321; 5683321 RGD 
Brain Hypoxia-Ischemia  IEP 5683321 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cast  (calpastatin)

Genes (Mus musculus)
Cast  (calpastatin)

Genes (Homo sapiens)
CAST  (calpastatin)


Additional Information