Loss of Ref-1 protein expression precedes DNA fragmentation in apoptotic neurons.

Ref-1 is a bifunctional protein that has been implicated in the transcriptional regulation of AP-1 elements and in DNA repair. To investigate whether Ref-1 is involved in programmed cell death its expression was measured in the 21-day-old rat brain at various time-points following a moderate unilateral hypoxic-ischemic (HI) insult. The CA1 pyramidal cells, which are selectively vulnerable to HI injury, showed a significant decrease in Ref-1 immunoreactivity 48 h-7 days post-insult. This loss of Ref-1 immunoreactivity may contribute to a decrease in endogenous repair activity and the development of apoptosis in the CA1 pyramidal cells.