Clusterin interaction with Bcl-xL is associated with seizure-induced neuronal death

Epilepsy Res. 2012 May;99(3):240-51. doi: 10.1016/j.eplepsyres.2011.12.002. Epub 2011 Dec 23.


Status epilepticus causes significant damage to the brain, and cellular injury due to prolonged seizures may cause the pathogenesis of epilepsy or cognitive deficits. Clusterin mediates several cell signaling pathways, including cell death or survival pathways in the brain. A nuclear form of clusterin protein has been suggested to have pro-apoptotic properties. Bcl-x(L) functions as a dominant-negative modulator of the pro-apoptotic protein Bax. However, the relationship between clusterin and Bcl-x(L) in cell death signaling in the brain remains unknown. Therefore, we examined whether clusterin interacts with Bcl-x(L) after seizures or whether this interaction is related to neuronal death. We found increased levels of nuclear clusterin and cleaved caspase-3 in CA3 neurons after prolonged seizures induced by systemic kainic acid, along with extensive hippocampal cell death, as evidenced by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and anti-active caspase-3 staining. Furthermore, co-immunoprecipitation and double immunofluorescence analyses revealed that clusterin interacted with Bcl-x(L) in dying CA3 neurons while the levels of Bcl-x(L), Bad or Bax remained constant. These findings provide evidence that nuclear clusterin signals cell death at least via an interaction with Bcl-x(L) in the hippocampus after seizures, suggesting that targeting nuclear clusterin may be a promising novel strategy to protect against seizure-induced neuronal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / physiology
  • Clusterin / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neurons / metabolism*
  • Neurons / pathology
  • Protein Binding / physiology
  • Seizures / metabolism*
  • Seizures / pathology
  • bcl-X Protein / metabolism*


  • Bcl2l1 protein, mouse
  • Clusterin
  • bcl-X Protein