Positive correlation between prolonged potentiation of binding of double-stranded oligonucleotide probe for the transcription factor AP1 and resistance to transient forebrain ischemia in gerbil hippocampus.
Gel retardation electrophoresis revealed that binding of a radiolabelled double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 was markedly potentiated in the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils with transient forebrain ischemia for 5 min, which is known to induce delayed death of pyramidal neurons exclusively in the CA1 subfield. The potentiation was transient in the vulnerable CA1 subfield, but persistent up to 18 h in the resistant CA3 subfield and dentate gyrus. However, no significant alteration was detected in endogenous levels of cyclic AMP response element binding protein phosphorylated at serine133 in these three different hippocampal structures 3 h after the reperfusion. On the other hand, hypothermia during ischemia which is known to protect the CA1 subfield against ischemic damages, led to a prolonged elevation of the activator protein-1 binding up to 9 h after the reperfusion in this vulnerable subfield at least in part through expression of c-Fos protein. Moreover, activator protein-1 binding was significantly elevated in the CA1 subfield up to 12 h after forebrain ischemia for 2 min which is shown not to induce marked damages to the vulnerable subfield. These results suggest that prolonged elevation of DNA binding activity of activator protein-1 may be responsible for molecular mechanisms underlying the unique vulnerability and/or resistance of particular subfields to a transient ischemic insult in the gerbil hippocampus.
Yoneda
Y
Y
Department of Pharmacology, Setsunan University, Hirakata, Osaka, Japan.
Azuma
Y
Y
Inoue
K
K
Ogita
K
K
Mitani
A
A
Zhang
L
L
Masuda
S
S
Higashihara
M
M
Kataoka
K
K
D033961:Adaptor Protein Complex 1; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D011869:Radioligand Assay; D014157:Transcription Factors / Q000378:metabolism*
D033961:Adaptor Protein Complex 1; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D009841:Oligonucleotides; D014157:Transcription Factors