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 present study, we demonstrate by in situ hybridization that transient global 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 pyramidal neurons of the hippocampus proper after 24 h, respectively. Immunohistochemical analysis revealed nuclear accumulation of Ref-l protein in granular cells of the ischemia-resistent dentate gyrus, whereas Ref-l 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, Out data suggest that oxidative stress induced by ischemia-reperfusion may increase neuronal ref-l expression. However, inability of ref-1 mRNA translation and nuclear translocation of encoded protein in CAI pyramidal neurons may inhibit repair of oxidative DNA damage or cellular adaptive responses leading to delayed neuronal cell death. (C) 1997 Elsevier Science B.V.