Document Detail


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.
MedLine Citation:
PMID:  19656264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rubén Martínez-Romero; Ana Cañuelo; Esther Martínez-Lara; Francisco Javier Oliver; Sara Cárdenas; Eva Siles
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-27
Journal Detail:
Title:  Journal of neurochemistry     Volume:  111     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-23     Completed Date:  2009-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  150-9     Citation Subset:  IM    
Affiliation:
Department of Experimental Biology. University of Jaén Paraje Las Lagunillas s/n, Jaén, Spain.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Anoxia* / metabolism,  pathology,  therapy
Antipyrine / analogs & derivatives,  pharmacology
Brain / drug effects,  metabolism*
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Transporter 2 / metabolism
Free Radical Scavengers / pharmacology
Gene Expression Regulation / drug effects,  physiology*
Hypoxia-Inducible Factor 1 / metabolism*
Isoquinolines / pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide / metabolism*
Oxidative Stress / drug effects,  physiology
Oxygen / pharmacology*,  therapeutic use
Piperidines / pharmacology
Poly(ADP-ribose) Polymerases / antagonists & inhibitors,  deficiency,  physiology*
RNA, Messenger / metabolism
Thiobarbituric Acid Reactive Substances / metabolism
Chemical
Reg. No./Substance:
0/3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone; 0/Enzyme Inhibitors; 0/Excitatory Amino Acid Transporter 2; 0/Free Radical Scavengers; 0/Hypoxia-Inducible Factor 1; 0/Isoquinolines; 0/Piperidines; 0/RNA, Messenger; 0/Thiobarbituric Acid Reactive Substances; 10102-43-9/Nitric Oxide; 60-80-0/Antipyrine; 7782-44-7/Oxygen; 89-25-8/phenylmethylpyrazolone; EC 2.4.2.30/Parp1 protein, mouse; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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