title: AP1 transcriptional factor activation and its relation to apoptosis of hippocampal CA1 pyramidal neurons after transient ischemia in gerbils.
abstract: The cellular processes with a potential to lead to delayed death of neurons following transient (5 min) ischemia in gerbil hippocampus were evaluated. Neuronal apoptosis, visualized by the terminal transferase dUTP nick-end labelling (TUNEL) reaction, selectively appeared in the CA1 region of the pyramidal cell layer between the third and fourth days after the insult. Concomitantly, an enhanced immunoreactivity to anti-cJun/AP1 (N) antibody as a major component of activator protein 1 (AP1) transcriptional factor was observed in CA1 neurons. In contrast, in the early postischemic phase, the cJun/AP1 reaction was noticed in numerous neurons and glia-like cells of the CA2/CA3 region, hilus of the dentate gyrus, and region of mossy fiber terminals. In parallel, hippocampal protein binding to AP1, measured by the electrophoretic mobility shift assay (EMSA), showed biphasic enhancement at 3 and then 72-120 hours after ischemia. Supershifts, with antibodies against c-Fos and phospho-c-Jun constituencies of the AP1 dimer, revealed an increased amount of phosphorylated c-Jun in the late postischemic phase. Collectively, these results suggest diversity of AP1 complex function, regulated by its dimer composition as well as time and place of expression during postischemic reperfusion. The early, survival-supporting AP1 response, located mainly in ischemia-resistant areas of CA2/3, is followed by the delayed phase, characteristic of massive neuronal apoptosis in CA1 with concomitant increase of phospho-c-Jun in AP1 dimer.
authors.affiliation: Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. kd-j@cmdik.pan.pl
authors.forename: K
authors.initials: K
authors.lastname: Domańska-Janik
authors.forename: P
authors.initials: P
authors.lastname: Bong
authors.forename: A
authors.initials: A
authors.lastname: Bronisz-Kowalczyk
authors.forename: H
authors.initials: H
authors.lastname: Zajac
authors.forename: B
authors.initials: B
authors.lastname: Zablocka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D017966:Pyramidal Cells / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D018808:Transcription Factor AP-1