Hypoxia-inducible factor-1 alpha mediates hypoxia-induced delayed neuronaldeath that involves p53

Citation
Mw. Halterman et al., Hypoxia-inducible factor-1 alpha mediates hypoxia-induced delayed neuronaldeath that involves p53, J NEUROSC, 19(16), 1999, pp. 6818-6824
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
19
Issue
16
Year of publication
1999
Pages
6818 - 6824
Database
ISI
SICI code
0270-6474(19990815)19:16<6818:HFAMHD>2.0.ZU;2-7
Abstract
Hypoxia-induced delayed neuronal death is known to require de novo gene exp ression; however, the molecular mediators that are involved remain undefine d. The transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha), in addition to promoting the expression of adaptive genes under conditions of hypoxia, has been implicated as being a necessary component in p53-medi ated cell death in tumors. Using herpes amplicon-mediated gene transfer in cortical neuronal cultures, we demonstrate that delivery of a dominant-nega tive form of HIF-1 alpha (HIFdn), capable of disrupting hypoxia-dependent t ranscription, reduces delayed neuronal death that follows hypoxic stress. I n contrast, hypoxia-resistant p53-null primary cultures are not protected b y HIFdn expression. These data indicate that, in hypoxic neurons, HIF-1 alp ha and p53 conspire to promote a pathological sequence resulting in cell de ath.