| ABCG2 reduces ROS-mediated toxicity and inflammation: a potential role in Alzheimer's disease. | |
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MedLine Citation:
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PMID: 20626554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alzheimer's disease is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition generates reactive-oxygen species (ROS), which are involved in Alzheimer's inflammatory and neurodegenerative pathology. We have previously observed that, in Alzheimer's disease brain, ABCG2 is up-regulated and AP-1 is activated, but NF-κB is not activated. In the present study, we examine the roles and mechanism of ABCG2 on ROS generation, inflammatory gene expression and signaling, heme homeostasis and Aβ production in cell models and on inflammatory signaling and Aβ deposition in Abcg2-knockout and wild-type mice. Our results show that ABCG2 plays a protective role against oxidative stress by decreasing ROS generation, enhancing antioxidant capacity, regulating heme level, and inhibiting inflammatory response in cell models. ABCG2 inhibits NF-κB activation but has less effect on AP-1 activation induced by ROS. This results in inhibition of interleukin-8 and growth-related oncogene (GRO) expression induced by ROS via NF-κB pathway. Abcg2 deficiency increased Aβ deposition and NF-κB activation in the brains of Abcg2-knockout mice compared with controls. These findings suggest that ABCG2 may relieve oxidative stress and inflammatory response via inhibiting NF-κB signaling pathway in cell models and brain tissues and thus may play a potential protective role in Alzheimer's neuroinflammatory response. |
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Authors:
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Shanshan Shen; Debbie Callaghan; Camille Juzwik; Huaqi Xiong; Peilin Huang; Wandong Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 114 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-24 Completed Date: 2010-10-19 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: 1590-604 Citation Subset: IM |
Copyright Information:
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© 2010 National Research Council of Canada. Journal Compilation © 2010 International Society for Neurochemistry. |
Affiliation:
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Department of Clinical Medicine, Southeast University, Nanjing, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
physiology* Alzheimer Disease / metabolism* Amyloid beta-Protein / metabolism Amyloid beta-Protein Precursor / metabolism Animals Brain / metabolism Cell Line Cell Line, Tumor Cell Survival Chemokine CXCL1 / biosynthesis Chemokine CXCL2 / biosynthesis Hemin / metabolism Humans Hydrogen Peroxide / toxicity Inflammation / metabolism Interleukin-8 / biosynthesis Mice Mice, Knockout NF-kappa B / metabolism Neoplasm Proteins / genetics, physiology* Peptide Fragments / metabolism Reactive Oxygen Species / metabolism* tert-Butylhydroperoxide / toxicity |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Abcg2 protein, mouse; 0/Amyloid beta-Protein; 0/Amyloid beta-Protein Precursor; 0/CXCL2 protein, human; 0/Chemokine CXCL1; 0/Chemokine CXCL2; 0/Interleukin-8; 0/NF-kappa B; 0/Neoplasm Proteins; 0/Peptide Fragments; 0/Reactive Oxygen Species; 0/amyloid beta-protein (1-40); 16009-13-5/Hemin; 75-91-2/tert-Butylhydroperoxide; 7722-84-1/Hydrogen Peroxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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