EXPRESSION OF NUCLEAR REDOX FACTOR REF-1 IN THE RAT HIPPOCAMPUS FOLLOWING GLOBAL-ISCHEMIA INDUCED BY CARDIAC-ARREST

The Ref-l protein is a bifunctional nuclear enzyme involved in repair of DNA lesions and in redox regulation of DNA-binding activity of BP-l family members, such as Fos and Jun transcription factors, Ln the pre sent study, we demonstrate by in situ hybridization that transient glo bal ischemia induced by cardiac arrest activates ref-l mRNA expression in the granular cells of the rat dentate gyrus after 6 h and in CA1 p yramidal neurons of the hippocampus proper after 24 h, respectively. I mmunohistochemical analysis revealed nuclear accumulation of Ref-l pro tein in granular cells of the ischemia-resistent dentate gyrus, wherea s Ref-l protein expression progressively decreased in vulnerable CA1 n eurons of the post-ischemic hippocampus from 24 h onwards. At the same time point, intense nuclear c-Jun immunoreactivity was observed in bo th neuronal cell populations, Out data suggest that oxidative stress i nduced by ischemia-reperfusion may increase neuronal ref-l expression. However, inability of ref-1 mRNA translation and nuclear translocatio n of encoded protein in CAI pyramidal neurons may inhibit repair of ox idative DNA damage or cellular adaptive responses leading to delayed n euronal cell death. (C) 1997 Elsevier Science B.V.