Induction of Apg-1, a member of the heat shock protein 110 family, following transient forebrain ischemia in the rat brain

Apg-1(Osp94) and apg-2 belong to the heat shock protein (hsp)110 family. In mouse somatic cells the apg-1 and hsp105/110 transcripts are inducible by a 32 degrees C to 39 degrees C heat shock, while apg-2 is not heat-inducible. Since ischemia is known to induce expression of hsp70, its effect on expression of apg-1 was assessed by using the 20-min forebrain ischemia model of the rat. In the cerebral cortex, Northern blot analysis and in situ hybridization histochemistry demonstrated an increased expression in neuronal cells of apg-1 transcripts 3 h after the onset of reperfusion, with a peak, at 12 h, followed by a decline. In the hippocampus, the level was increased at 3 h, remained constant until 24 h, and then declined. Transcript levels of apg-2 as well as hsp105 were also increased under the present conditions, indicating that the expression of apg-2 was differentially regulated in response to heat and ischemic stresses. The induction kinetics of hsp105, but neither apg-2 nor hsp70, were identical to those of apg-1. These results demonstrated that brain ischemia/reperfusion induced expression of each member of the hsp110 family, although the regulatory mechanisms may not be the same. They also suggest a significant role of apg-1 in both the ischemic-and heat-stress responses and in the normal functioning of the non-stressed neuronal cells. (C) 1998 Academic Press.