Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain
Br. Hu et al., Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain, NEUROSCIENC, 89(2), 1999, pp. 437-452
The transcription factors cyclic AMP responsive element-binding protein (CR
EB) and activating transcription factor-2 were studied in rat brains subjec
ted to 15 min ischemia followed by varied periods of reperfusion using west
ern blot and immunocytochemical analyses. The total amounts of both CREB an
d activating transcription factor-2 were not altered in the hippocampus aft
er ischemia. In contrast, levels of the phosphorylated forms of both transc
ription factors decreased during ischemia but rebounded following reperfusi
on. The phospho-forms of CREB and activating transcription factor-2 showed
regional and temporal differences in their expression. Phospho-CREB was inc
reased relative to control levels at 30 min, and continued to increase for
at least three days postischemia, mainly in dentate granule cells. The leve
l of phospho-activating transcription factor-2 appeared to be higher in CA1
pyramidal cells than in dentate granule cells after ischemia.
The present findings suggest that the signaling pathways for phosphorylatio
n of CREB may be neuroprotective for dentate cells, which are relatively re
sistant to ischemic insults. The increased phospho-activating transcription
factor-2 may reflect increased stresses in these neurons. The more modest
activation of CREB pathways in CA1 neurons may not be enough to overcome th
e increased stresses in these neurons, contributing to delayed neuronal dea
th. (C) 1998 IBRO. Published by Elsevier Science Ltd.