Effect of 3-aminobenzamide on Bcl-2, Bax and AIF localization in hippocampal neurons altered by ischemia-reperfusion injury. the immunocytochemical study

Acta Neurobiol Exp (Wars). 2006;66(1):15-22. doi: 10.55782/ane-2006-1583.

Abstract

Poly(ADP-ribose) polymerase plays an important role in cell survival and death. Our previous histological and ultrastructural studies showed that PARP inhibitor 3-aminobenzamide (3-AB) protected neurons against death after ischemia. In this study we investigated the effect of 3-AB on the localization and expression of apoptosis inducing factor (AIF) and on two proteins from Bcl-2 family: Bcl-2 and Bax in hippocampal area CA1, on the 4th day after 3 min of forebrain ischemia in gerbils. Our results indicated that after ischemia AIF is preferentially translocated from the mitochondria to the cytoplasm and to the nucleus. Intravenous administration of 3-AB (30 mg/kg b.w.) prevents AIF translocation to the nucleus. AIF was mainly seen in the structurally unchanged mitochondria and Golgi complex. Moreover, after 3-AB administration overexpression of Bcl-2 protein was observed in mitochondrial membranes, rough endoplasmatic reticulum, Golgi complex, nuclear envelopes, and also in cytoplasm and in nucleus. These data suggest that inhibition of PARP activity may have a beneficial effect on hippocampal neurons through overexpression of Bcl-2 protein and suppression of AIF translocation to the nucleus.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Inducing Factor / metabolism*
  • Benzamides / pharmacology*
  • Disease Models, Animal
  • Gerbillinae
  • Hippocampus / pathology*
  • Immunohistochemistry / methods
  • Male
  • Microscopy, Immunoelectron / methods
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / classification
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / prevention & control
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Apoptosis Inducing Factor
  • Benzamides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • 3-aminobenzamide
  • Poly(ADP-ribose) Polymerases