| Tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 mediate cerebral ischemia-induced poly(ADP-ribose) polymerase-1 activation and neuronal death. | |
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MedLine Citation:
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PMID: 20955770 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Fn14) are expressed in neurons. Here we demonstrate that TWEAK induces a dose-dependent increase in neuronal death and that this effect is independent of tumor necrosis factor alpha (TNF-α) and mediated by nuclear factor-kappa B (NF-κB) pathway activation. Incubation with TWEAK induces apoptotic cell death in wild-type (Wt) but not in Fn14 deficient (Fn14(-/-)) neurons. Intracerebral injection of TWEAK induces accumulation of poly(ADP-ribose) polymers (PAR) in Wt but not in Fn14(-/-) mice. Exposure to oxygen-glucose deprivation (OGD) conditions increases TWEAK and Fn14 mRNA expression in Wt neurons, and decreases cell survival in Wt but not in Fn14(-/-) or TWEAK deficient (TWEAK(-/-)) neurons. Experimental middle cerebral artery occlusion (MCAO) increases the expression of TWEAK and Fn14 mRNA and active caspase-3, and the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1) with accumulation of PAR in the ischemic area in Wt but not Fn14(-/-) mice. Together, these results suggest a model where in response to hypoxia/ischemia the interaction between TWEAK and Fn14 in neurons induces PARP-1 activation with accumulation of PAR polymers and cell death via NF-κB pathway activation. This is a novel pathway for hypoxia/ischemia-induced TWEAK-mediated cell death and a potential therapeutic target for ischemic stroke. |
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Authors:
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W B Haile; R Echeverry; F Wu; J Guzman; J An; J Wu; M Yepes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-16 |
Journal Detail:
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Title: Neuroscience Volume: 171 ISSN: 1873-7544 ISO Abbreviation: Neuroscience Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-03-10 Revised Date: 2012-01-10 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 1256-64 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / pathology Cell Death / drug effects, genetics Cells, Cultured Cerebral Cortex / cytology Disease Models, Animal Dose-Response Relationship, Drug Embryo, Mammalian Gene Expression Regulation / drug effects, genetics Glucose / deficiency Hydrogen Peroxide / pharmacology Infarction, Middle Cerebral Artery / enzymology*, pathology*, physiopathology Mice Mice, Knockout Neurons / drug effects, physiology* Oxidants / pharmacology Poly(ADP-ribose) Polymerases / metabolism* Receptors, Tumor Necrosis Factor / deficiency, metabolism Signal Transduction / drug effects, genetics Tumor Necrosis Factor-alpha / pharmacology Tumor Necrosis Factors / deficiency, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-095063/HL/NHLBI NIH HHS; NS-062073/NS/NINDS NIH HHS; R01 NS062073-01A2/NS/NINDS NIH HHS; R01 NS062073-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oxidants; 0/Receptors, Tumor Necrosis Factor; 0/TWEAK receptor; 0/Tnfsf12 protein, mouse; 0/Tumor Necrosis Factor-alpha; 0/Tumor Necrosis Factors; 50-99-7/Glucose; 7722-84-1/Hydrogen Peroxide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.30/poly(ADP-ribose)polymerase-1, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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