Multiple apoptogenic proteins are involved in the nuclear translocation of Apoptosis Inducing Factor during transient focal cerebral ischemia in rat

Ganta Vijay Chaitanya, Phanithi Prakash Babu

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Apoptosis Inducing Factor is a mitochondrial protein which upon translocation to nucleus causes large scale DNA fragmentation. The stimulus for the cytosolic release and nuclear translocation for this protein still remains to be understood. The role of calpains, cathepsin-b, Poly ADP (ribose) Polymerase and granzyme-b in the nuclear translocation of AIF has been investigated in the pathology of cerebral ischemia. Calpains, cathepsin-b and PARP-1 which were mostly confined to cytosol, lysosomes and nucleus respectively were found to be elevated in the mitochondrial fraction interacting with AIF in the western blot analysis and double immunofluorescence analysis. Western blot and immunohistochemical analysis revealed elevated levels of granzyme-b secreted by cytotoxic T lymphocytes and natural killer cells in the infarct of ischemic mouse brain. Co-immunoprecipitation revealed and western blot analysis the interaction and break down of Heat Shock Protein-70 an endogenous inhibitor of AIF into signature fragments by granzyme-b facilitating the nuclear translocation of AIF. Break down of HSP-70 correlated with the nuclear translocation of AIF observed in western and immunohistochemical analysis. These results indicate that multiple proteases were involved in the nuclear translocation of AIF during the pathology of cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)178-190
Number of pages13
JournalBrain Research
Volume1246
DOIs
StatePublished - Dec 30 2008
Externally publishedYes

Keywords

  • Apoptosis Inducing Factor
  • Calpain
  • Cathepsin-b
  • Cerebral ischemia
  • Granzyme-b
  • Heat Shock Protein-70
  • Poly ADP (ribose) Polymerase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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