Dynamic changes in the composition of the AP-1 transcription factor DNA-binding activity in rat brain following kainate-induced seizures and cell death.
Kainate, a potent excitatory and neurotoxic agent, has also proved useful in studies on other glutamate-driven phenomena, such as neuronal plasticity. Long-term effects of kainate are apparently dependent on its influence on the expression of various genes, including those encoding the AP-1 transcription factor, consisting of proteins belonging to the Fos and Jun families. In our studies we analysed c-fos, fos B, c-jun, jun B and jun D mRNA levels as well as a functional feature of AP-1, its DNA-binding activity, in the rat brain following systemic injection of kainate. Two phases of elevated AP-1 DNA-binding activity were observed in the hippocampus and entorhinal cortex, and were correlated with period of seizures (2 and 6 h after kainate injection) and neuron damage (48-72 h). At 72 h after kainate treatment DNA fragmentation, believed to be diagnostic of apoptotic processes typical of programmed cell death phenomena, was noted. Two and six hours after the treatment, AP-1 consisted predominantly of Fos B, c-Fos, Fra-2 and Jun B, while at 72 h Jun D constituted the major AP-1 component in place of Jun B, and no c-Fos was detected. Only a slight AP-1 increase was seen 24 h after kainate treatment. In the sensory cortex, only the late phase of AP-1 elevation was detected. Contrary to AP-1, no effect of kainate on levels of two other transcription factors, CREB/ATF (cAMP-responsive element binding proteins) and OCT (octamer element DNA-binding activity) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Nencki Institute of Experimental Biology, Warsaw, Poland.
B
B
Kaminska
R K
RK
Filipkowski
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G
Zurkowska
W
W
Lason
R
R
Przewlocki
L
L
Kaczmarek
D000818:Animals; D001921:Brain / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007608:Kainic Acid; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D018808:Transcription Factor AP-1; D007608:Kainic Acid