| The role of PARP activation in glutamate-induced necroptosis in HT-22 cells. | |
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MedLine Citation:
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PMID: 20451505 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Oxidative cell death contributes to neuronal cell death in many neurological diseases such as stroke, brain trauma, and Alzheimer's disease. In this study, we explored the involvement of poly(ADP-ribose)-polymerase (PARP) in oxidative stress-induced necroptosis. We showed that PJ34, a potent and specific inhibitor of PARP, can completely inhibit glutamate-induced necroptosis in HT-22 cells. This protective effect was still observed 8h after glutamate exposure followed by PJ34 treatment. These results suggest that PARP activation plays a critical role in glutamate-induced necroptosis. We also examined the interaction between PARP and a necroptosis inhibitor called necrostatin-1 (Nec-1). Previously, we showed that Nec-1 protects against glutamate-induced oxytosis by inhibiting the translocation of cellular apoptosis-inducing factor (AIF), a downstream target of PARP-1 activation. In this study, Nec-1 reduced PARP activity but had no effect on the expression of PARP-1 in cells treated with glutamate. Nec-1 also did not protect against cell death mediated by the PARP activator N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), although PJ34 did protect against MNNG-mediated cell death. These findings suggest that Nec-1 is not a direct PARP inhibitor and that its signaling target is located upstream of PARP. |
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Authors:
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Xingshun Xu; Chu C Chua; Min Zhang; Deqin Geng; Chun-Feng Liu; Ronald C Hamdy; Balvin H L Chua |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-06 |
Journal Detail:
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Title: Brain research Volume: 1343 ISSN: 1872-6240 ISO Abbreviation: Brain Res. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 206-12 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou City, Jiangsu Province 215123, PR China. Xingshunxu@suda.edu.cn |
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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HL087271/HL/NHLBI NIH HHS; HL096099/HL/NHLBI NIH HHS |
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