Transient cerebral ischemia induces delayed proapoptotic Bad translocation to mitochondria in CA1 sector of hippocampus

Brain Res Mol Brain Res. 2005 Feb 18;133(2):274-80. doi: 10.1016/j.molbrainres.2004.10.013.

Abstract

Delayed ischemic brain damage is associated with mitochondrial dysfunction, but the underlying mechanisms are not known in detail. Recent data suggest that the process is associated with multidirectional changes in the activities of various proteins located in mitochondria. Of these, the stress-activated kinase JNK is delay-activated postischemia. We induced 5 min cerebral ischemia in gerbils followed by 3, 24, 48, 72 and 96 h of reperfusion. Here we show the postischemic translocation of proapoptotic protein Bad to mitochondria. Immunoelectron microscopic examination revealed the co-appearance of Bad and Bcl-2 proteins in postischemic mitochondria in ischemia-vulnerable CA1 sector of hippocampus as opposed to the ischemia-resistant DG region. Mitochondrial increase of Bad protein is coincident with a transient decrease of the active, phosphorylated form of prosurvival kinase, Raf-1, under conditions of long reperfusion. The above demonstrated sequence of events is likely to play a role in delayed postischemic nerve cell death.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Carrier Proteins / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation / physiology
  • Gerbillinae
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Ischemic Attack, Transient / metabolism*
  • Male
  • Microscopy, Immunoelectron / methods
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Protein Transport / physiology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Reperfusion / methods
  • Time Factors
  • bcl-Associated Death Protein

Substances

  • Carrier Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-Associated Death Protein
  • Proto-Oncogene Proteins c-raf