| 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. | |
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MedLine Citation:
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PMID: 19656264 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Rubén Martínez-Romero; Ana Cañuelo; Esther Martínez-Lara; Francisco Javier Oliver; Sara Cárdenas; Eva Siles |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 111 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-23 Completed Date: 2009-10-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 150-9 Citation Subset: IM |
Affiliation:
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Department of Experimental Biology. University of Jaén Paraje Las Lagunillas s/n, Jaén, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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