Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia.
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.
Van Hoecke
Michaël
M
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Faculté de Pharmacie, 7 boulevard Jeanne d'Arc, BP 87900, 21079 Dijon Cedex, France.
Prigent-Tessier
Anne S
AS
Garnier
Philippe E
PE
Bertrand
Nathalie M
NM
Filomenko
Rodolphe
R
Bettaieb
Ali
A
Marie
Christine
C
Beley
Alain G
AG
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020767:Intracranial Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000378:metabolism* / Q000503:physiopathology
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D053148:Caspase 3; D010100:Oxygen