Rapid potentiation of DNA binding activities of particular transcription factors with leucine-zipper motifs in discrete brain structures of the gerbil with transient forebrain ischemia.
Binding of radiolabeled double stranded oligonucleotide probes for nuclear transcription factors with leucine-zipper motifs, such as activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and Myc, was unevenly distributed in gerbil brain in a manner peculiar to each factor. Among 3 different hippocampal subfields examined, the dentate gyrus had the highest basal DNA binding activities of AP1 with progressively less potent binding in the CA3 and CA1 subfields. Similarly, the dentate gyrus was highest in the basal binding of probes for both CREB and Myc among the 3 distinct hippocampal subregions. However, transient forebrain ischemia for 5 min induced more potent enhancement of the AP1 binding in the CA1 subfield 4 h after the insult than in the CA3 subfield and dentate gyrus. In contrast, the ischemic injury similarly tripled DNA binding activities of CREB without markedly affecting those of Myc in hippocampal CA1 and CA3 subfields. Binding of the probe for AP1 was also markedly potentiated following ischemia in the thalamus, caudate putamen, frontal cortex and cerebellar cortex in a rank order of decreasing magnitude, while the ischemic insult induced slight but statistically significant potentiation of both CREB and Myc binding in the thalamus without affecting that in other discrete brain regions. These results suggest that expression of AP1 may be a determinant of unique vulnerability and/or resistance to an ischemic insult in the gerbil hippocampus.
Yoneda
Y
Y
Department of Pharmacology, Setsunan University, Osaka, Japan.
Ogita
K
K
Inoue
K
K
Mitani
A
A
Zhang
L
L
Masuda
S
S
Higashihara
M
M
Kataoka
K
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D001667:Binding, Competitive; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D016350:Leucine Zippers / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D016548:Prosencephalon / Q000098:blood supply* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D016271:Proto-Oncogene Proteins c-myc; D018808:Transcription Factor AP-1; D004247:DNA