Identification and characterization of PEBP as a calpain substrate

Qinghua Chen, Susan Wang, Stephanie N. Thompson, Edward D. Hall, Rodney P. Guttmann

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Calpains are calcium- and thiol-dependent proteases whose dysregulation has been implicated in a number of diseases and conditions such as cardiovascular dysfunction, ischemic stroke, and Alzheimer's disease (AD). While the effects of calpain activity are evident, the precise mechanism(s) by which dysregulated calpain activity results in cellular degeneration are less clear. In order to determine the impact of calpain activity, there is a need to identify the range of specific calpain substrates. Using an in vitro proteomics approach we confirmed that phosphatidylethanolamine-binding protein (PEBP) as a novel in vitro and in situ calpain substrate. We also observed PEBP proteolysis in a model of brain injury in which calpain is clearly activated. In addition, with evidence of calpain dysregulation in AD, we quantitated protein levels of PEBP in postmortem brain samples from the hippocampus of AD and age-matched controls and found that PEBP levels were approximately 20% greater in AD. Finally, with previous evidence that PEBP may act as a serine protease inhibitor, we tested PEBP as an inhibitor of the proteasome and found that PEBP inhibited the chymostrypsin-like activity of the proteasome by ∼30%. Together these data identify PEBP as a potential in vivo calpain substrate and indicate that increased PEBP levels may contribute to impaired proteasome function.

Original languageEnglish
Pages (from-to)1133-1141
Number of pages9
JournalJournal of Neurochemistry
Issue number4
StatePublished - Nov 2006


  • Alzheimer's disease
  • Calpain
  • Phosphatidylethanolamine-binding protein
  • Proteasome

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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