Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a transcription factor that was suggested in vitro to promote cell death by modulation of proapoptotic genes. In this report, we tested the hypothesis of an in vivo proapoptotic role of HIF-1 alpha after an ischemic insult. For this purpose, HIF-1 alpha and procaspase-3 mRNA and protein expressions were examined in rat brain subjected to 12- and 24-h permanent focal ischemia and the presence of an HIF-1 binding activity to the caspase-3 gene promoter was explored. The results showed that HIF-1 alpha and procaspase-3 expressions increased with a similar pattern in response to ischemia. In addition, caspase-3 activation was observed in cells that express HIF-1 alpha. Moreover, electrophoretic mobility assay revealed a specific HIF-1 binding activity to the caspase-3 gene promoter. Altogether the present data provide strong arguments for a causative relationship between HIF-1 alpha and caspase-3 inductions through a functional binding activity to the caspase-3 gene promoter. (c) 2006 Elsevier Inc. All rights reserved.