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Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction.

Abstract：

:Global forebrain ischemia of 5-min duration results in delayed neuronal death (DND) of CA1 neurons in the gerbil hippocampus. DND can be prevented by a preconditioning sublethal ischemic stimulus (2. 5 min), a phenomenon, known as ischemic tolerance induction. Striking evidence exists for the involvement of regulatory transcription factors encoded by immediate early genes (IEGs) in the fate of CA1 neurons. Here, we investigated by electrophoretic mobility shift assay (EMSA) the postischemic changes of the DNA binding activity of the Activator Protein-1 (AP-1) transcription factor complex after preconditioning, lethal ischemia, and after acquisition of an ischemic tolerant state. A short duration peak of AP-1 binding activity at 3 h of reperfusion was a hallmark of ischemic tolerance induction. The kinetics of this activation profile, i.e. the rapid linear increase between 1 and 3 h and a similar rapid decline at 6 or 12 h of reperfusion are prominent within the CA1 and CA3 region of all ischemic groups which are designated for neuronal survival. No changes in the c-Jun and ATF-2 immunoreactivity were observed in the CA1 region, however an increase in only c-Jun immunoreactivity occurred in concordance with the elevation of AP-1 binding in the CA3 region. The results clearly demonstrate a differential regulation of AP-1 binding activity in CA1 during and after acquisition of an ischemic tolerant state in contrast to ischemia leading to neuronal death. The early peak at 3 h of reperfusion in AP-1 binding affinity observed in the single 2.5 min and the ischemic tolerant groups suggests a protective role of early AP-1 activation, whereas failure of this initial activation may contribute to DND. Our data furthermore suggest, that elevation of the AP-1 binding activity in the CA1 and CA3 regions underlies a different regulatory mechanism in the gerbil hippocampus after ischemic stress.

journal_name

Brain Res

journal_title

Brain research

authors

Kapinya K,Penzel R,Sommer C,Kiessling M

doi

10.1016/s0006-8993(00)02503-8

subject

Has Abstract

pub_date

2000-07-28 00:00:00

pages

282-93

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(00)02503-8

journal_volume

872

pub_type

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Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction.