Calpain cleaves methionine aminopeptidase-2 in a rat model of ischemia/reperfusion

Tiffanie Clinkinbeard, Sarbani Ghoshal, Susan Craddock, L. Creed Pettigrew, Rodney P. Guttmann

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Ischemic stroke results in multiple injurious signals within a cell including dysregulation of calcium homeostasis. Consequently, there is an increase in the enzymatic activity of the calpains, calcium dependent proteases that are thought to contribute to neuronal injury. In addition, cellular stress due to ischemia/reperfusion also triggers a decrease in protein translation through activation of the unfolded protein response (UPR). In the present study we found that methionine aminopeptidase 2 (MetAP2), a critical component of the translation initiation complex, is a calpain substrate. In vitro calpain assays demonstrated that while MetAP2 has autoproteolytic activity, calpain also produces a stable proteolytic fragment at 50 kDa using recombinant MetAP2. This 50 kDa fragment, in addition to a 57 kDa fragment was present in in vitro digestions of rat brain homogenates. Production of these fragments was inhibited by calpastatin, the endogenous and specific inhibitor of calpain. Using an in vivo middle cerebral artery occlusion (MCAO) model only the 57 kDa fragment of MetAP2 was observed. These data suggest that calpain activation in stroke may regulate MetAP2-mediated protein translation giving calpains a larger role in the cellular stress response than previously determined.

Original languageEnglish
Pages (from-to)129-135
Number of pages7
JournalBrain Research
StatePublished - Mar 7 2013

Bibliographical note

Funding Information:
This work was supported by Grant NIH P01 NS058484.


  • Calcium
  • Calpain
  • MetAP2
  • Methionine aminopeptidase 2
  • P67
  • Protease
  • Stroke
  • Unfolded protein response

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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