Alteration of transcription factor binding activities in the ischemic rat brain.

Transient focal ischemia-reperfusion in the cerebral cortex caused regional alteration of DNA-binding activities of transcription factors AP-1, CREB, Sp-1, and NF-kB. The changes were time-dependent. During the first 24 hr of reperfusion after 90 min ischemia, there was an increase in the binding activity of AP-1 only in the region surrounding the ischemic cortex. Five days after ischemia, an increase in the binding activities of CREB, Sp-1, and NF-kB, but not AP-1, was noted in the ischemic cortex, and to a lesser extent, Sp-1 and NF-kB, in the surrounding region. The binding activities of these transcription factors were reduced by hydrogen peroxide but could be restored by dithiothreitol and 2-mercaptoethanol. These results are the first demonstration of ischemia-induced differential regulation of transcription factor binding activities which are time-, region-, and redox state dependent.