Expression of nuclear redox factor ref-1 in the rat hippocampus following global ischemia induced by cardiac arrest.
The Ref-1 protein is a bifunctional nuclear enzyme involved in repair of DNA lesions and in redox regulation of DNA-binding activity of AP-1 family members, such as Fos and Jun transcription factors. In the present study, we demonstrate by in situ hybridization that transient global ischemia induced by cardiac arrest activates ref-1 mRNA expression in the granular cells of the rat dentate gyrus after 6 h and in CA1 pyramidal neurons of the hippocampus proper after 24 h, respectively. Immunohistochemical analysis revealed nuclear accumulation of Ref-1 protein in granular cells of the ischemia-resistant dentate gyrus, whereas Ref-1 protein expression progressively decreased in vulnerable CA1 neurons of the post-ischemic hippocampus from 24 h onwards. At the same time point, intense nuclear c-Jun immunoreactivity was observed in both neuronal cell populations. Our data suggest that oxidative stress induced by ischemia-reperfusion may increase neuronal ref-1 expression. However, inability of ref-1 mRNA translation and nuclear translocation of encoded protein in CA1 pyramidal neurons may inhibit repair of oxidative DNA damage or cellular adaptive responses leading to delayed neuronal cell death.
Gillardon
F
F
Max-Planck-Institut für Neurologische Forschung, Köln, Germany. gillardon@mpin-koeln.mpg.de
Böttiger
B
B
Hossmann
K A
KA
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D019757:Carbon-Oxygen Lyases; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014158:Transcription, Genetic
D005904:Glial Fibrillary Acidic Protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D019757:Carbon-Oxygen Lyases; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase