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

Mol Cell Neurosci. 2007 Jan;34(1):40-7. doi: 10.1016/j.mcn.2006.09.009. Epub 2006 Nov 13.


Hypoxia-inducible factor 1 alpha (HIF-1alpha) 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-1alpha after an ischemic insult. For this purpose, HIF-1alpha 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-1alpha 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-1alpha. 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-1alpha and caspase-3 inductions through a functional binding activity to the caspase-3 gene promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Disease Models, Animal
  • Enzyme Activation / genetics
  • Gene Expression Regulation, Enzymologic / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Hypoxia-Ischemia, Brain / genetics
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / physiopathology
  • Intracranial Thrombosis / genetics
  • Intracranial Thrombosis / metabolism*
  • Intracranial Thrombosis / physiopathology
  • Male
  • Oxygen / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Binding / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Telencephalon / metabolism*
  • Telencephalon / physiopathology


  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Caspase 3
  • Oxygen