Inhibition of calpain-mediated cell death by a novel peptide inhibitor

Adrian T. McCollum, Faegheh Jafarifar, Bert C. Lynn, Remigius U. Agu, Audra L. Stinchcomb, Susan Wang, Qinghua Chen, Rodney P. Guttmann

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Calpains are calcium- and thiol-dependent proteases whose overactivation and degradation of various substrates have been implicated in a number of diseases and conditions such as cardiovascular dysfunction and ischemic stroke. With increasing evidence for calpain's role in cellular damage, the development of calpain inhibitors continues to be an important objective. Previously, we identified a highly specific calcium-dependent, calpain interacting peptide L-S-E-A-L, that showed homology to domains A and C of the only known endogenous inhibitor of calpains, calpastatin. This suggested that LSEAL had a calpain inhibitory function and synthetic LSEAL inhibited calpain I and II proteolysis of two calpain substrates, tau and alpha-synuclein. In the present study, we demonstrate that synthetic LSEAL is membrane permeable and is a potent inhibitor in two established models of calpain-mediated cell death using primary rat cortical neurons and SH-SY5Y neuroblastoma cells. In addition, we show that LSEAL inhibits calpain activity towards protein substrates as detected by an antibody to a calpain-specific breakdown product of spectrin. Taken together, these results suggest that LSEAL may represent a novel calpastatin mimetic with the potential for benefit in conditions of increased calpain activity such as stroke, traumatic brain injury or heart attack.

Original languageEnglish
Pages (from-to)506-513
Number of pages8
JournalExperimental Neurology
Issue number2
StatePublished - Dec 2006

Bibliographical note

Funding Information:
The authors would like to thank Drs. Jeff Keller and Harry Levine for materials and technical assistance and MatTek Corporation for kindly providing the EpiAirway™ tissue samples. Supported by grants from the NIH (NS047635–RPG) and the AHA (0335233N–RPG).


  • Calcium
  • Calpain
  • Cell death
  • Peptide
  • Phage-display

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


Dive into the research topics of 'Inhibition of calpain-mediated cell death by a novel peptide inhibitor'. Together they form a unique fingerprint.

Cite this