Effect of 3-aminobenzamide on Bcl-2, Bax and AIF localization in hippocampal neurons altered by ischemia-reperfusion injury. the immunocytochemical study.
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.
Strosznajder
Robert
R
Department of Respiratory Research, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. roberts@cmdik.pan.pl.
Gajkowska
Barbara
B
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000145:classification / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D051033:Apoptosis Inducing Factor; D001549:Benzamides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases