Your browser doesn't support javascript.
loading
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.
Martínez-Romero, Rubén; Cañuelo, Ana; Martínez-Lara, Esther; Javier Oliver, Francisco; Cárdenas, Sara; Siles, Eva.
Afiliação
  • Martínez-Romero R; Department of Experimental Biology. University of Jaén Paraje Las Lagunillas s/n, Jaén, Spain.
J Neurochem ; 111(1): 150-9, 2009 Oct.
Article em En | MEDLINE | ID: mdl-19656264
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxigênio / Encéfalo / Regulação da Expressão Gênica / Poli(ADP-Ribose) Polimerases / Fator 1 Induzível por Hipóxia / Hipóxia / 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

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxigênio / Encéfalo / Regulação da Expressão Gênica / Poli(ADP-Ribose) Polimerases / Fator 1 Induzível por Hipóxia / Hipóxia / 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