Poly(ADP-ribose) polymerase-1 modulation of in vivo response of brain hypoxia-inducible factor-1 to hypoxia/reoxygenation is mediated by nitric oxide and factor inhibiting HIF.
J Neurochem
; 111(1): 150-9, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19656264
ABSTRACT
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that once activated by genotoxic agents, modulates its own activity and that of several other nuclear proteins. The absence or pharmacological inhibition of this protein has been proven to be beneficial in the treatment of different diseases involving a hypoxic situation. We previously reported that PARP-1 modulates the hypoxia-inducible factor-1 (HIF-1) response in vitro, but this effect has not yet been demonstrated in vivo. The brain is especially susceptible to hypoxic injury, and the present study demonstrates that PARP-1 plays a major role in the post-hypoxic response of HIF-1alpha in the cerebral cortex. Immediate post-hypoxic HIF-1alpha accumulation was higher in the presence of PARP-1, and this differential response was mediated by nitric oxide and to a lesser extent, reactive oxygen species. PARP-1 was also found to induce a more rapid but less sustained HIF-1 transcriptional activity by up-regulating the factor inhibiting HIF. The implication of PARP-1 in these results was further demonstrated by pharmacologically inhibiting PARP in wild-type mice. In conclusion, our data suggest that PARP-1 has an important regulatory role in the in vivo response of brain HIF-1 to hypoxia/reoxygenation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Encéfalo
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Regulação da Expressão Gênica
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Poli(ADP-Ribose) Polimerases
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Fator 1 Induzível por Hipóxia
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Hipóxia
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Óxido Nítrico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Espanha