Bax-inhibiting peptide protects glutamate-induced cerebellar granule cell death by blocking Bax translocation

Neurosci Lett. 2009 Feb 13;451(1):11-5. doi: 10.1016/j.neulet.2008.12.021. Epub 2008 Dec 24.


Glutamate-induced excitotoxicity has been implicated in the pathogenesis of various neurological damages and disorders. In the brain damage of immature animals such as neonatal hypoxic-ischemic brain injury, the excitotoxicity appears to be more intimately involved through apoptosis. Bax, a member of the Bcl-2 family proteins, plays a key role in the promotion of apoptosis by translocation from the cytosol to the mitochondria and the release of apoptogenic factors such as cytochrome c. Recently, Bax-inhibiting peptide (BIP), a novel membrane-permeable peptide which can bind Bax in the cytosol and inhibit its translocation to the mitochondria, was developed. To investigate the possibility of a new neuroprotection strategy targeting Bax translocation in glutamate-induced neuronal cell death, cerebellar granule neurons (CGNs) were exposed to glutamate with or without BIP. Pretreatment of CGNs with BIP elicited a dose-dependent reduction of glutamate-induced neuronal cell death as measured by MTT assay. BIP significantly suppressed both the number of TUNEL-positive cells and the increase in caspases 3 and 9 activities induced by glutamate. In addition, immunoblotting after subcellular fractionation revealed that BIP prevented the glutamate-induced Bax translocation to the mitochondria and the release of cytochrome c from the mitochondria. These results suggest that agents capable of inhibiting Bax activity such as BIP might lead to new drugs for glutamate-related diseases in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspases / drug effects
  • Caspases / metabolism
  • Cerebellum
  • Cytochromes c / metabolism
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism
  • Glutamic Acid / toxicity*
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology
  • In Situ Nick-End Labeling
  • Indicators and Reagents
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazolium Salts
  • bcl-2-Associated X Protein / antagonists & inhibitors*
  • bcl-2-Associated X Protein / metabolism


  • Bax-inhibiting peptide, BIP
  • Indicators and Reagents
  • Neuroprotective Agents
  • Oligopeptides
  • Peptides
  • Tetrazolium Salts
  • bcl-2-Associated X Protein
  • Glutamic Acid
  • Cytochromes c
  • Caspases