| Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells. | |
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MedLine Citation:
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PMID: 18676681 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The physicochemical properties of nanomaterials differ from those of the bulk material of the same composition. However, little is known about the underlying effects of these particles in carcinogenesis. The purpose of this study was to determine the mechanisms involved in the carcinogenic properties of nanoparticles using aluminum oxide (Al(2)O(3)/alumina) nanoparticles as the prototype. Well-established mouse epithelial JB6 cells, sensitive to neoplastic transformation, were used as the experimental model. We demonstrate that alumina was internalized and maintained its physicochemical composition inside the cells. Alumina increased cell proliferation (53%), proliferating cell nuclear antigen (PCNA) levels, cell viability and growth in soft agar. The level of manganese superoxide dismutase, a key mitochondrial antioxidant enzyme, was elevated, suggesting a redox signaling event. In addition, the levels of reactive oxygen species and the activities of the redox sensitive transcription factor activator protein-1 (AP-1) and a longevity-related protein, sirtuin 1 (SIRT1), were increased. SIRT1 knockdown reduces DNA synthesis, cell viability, PCNA levels, AP-1 transcriptional activity and protein levels of its targets, JunD, c-Jun and BcL-xl, more than controls do. Immunoprecipitation studies revealed that SIRT1 interacts with the AP-1 components c-Jun and JunD but not with c-Fos. The results identify SIRT1 as an AP-1 modulator and suggest a novel mechanism by which alumina nanoparticles may function as a potential carcinogen. |
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Authors:
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Swatee Dey; Vasudevan Bakthavatchalu; Michael T Tseng; Peng Wu; Rebecca L Florence; Eric A Grulke; Robert A Yokel; Sanjit Kumar Dhar; Hsin-Sheng Yang; Yumin Chen; Daret K St Clair |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-08-01 |
Journal Detail:
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Title: Carcinogenesis Volume: 29 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-02 Completed Date: 2008-10-14 Revised Date: 2011-05-02 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 1920-9 Citation Subset: IM |
Affiliation:
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Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Health Sciences Research Building 454, Lexington, KY 40536-0298, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aluminum Oxide
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toxicity* Animals Apoptosis / drug effects Carcinogens / toxicity* Cell Proliferation / drug effects Cell Transformation, Neoplastic Epithelial Cells / drug effects Mice Nanoparticles / chemistry, toxicity* Proliferating Cell Nuclear Antigen / analysis Reactive Oxygen Species / metabolism Sirtuin 1 Sirtuins / physiology* Skin / drug effects*, metabolism, pathology Superoxide Dismutase / analysis Transcription Factor AP-1 / physiology* bcl-X Protein / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CA 49797/CA/NCI NIH HHS; CA 73599/CA/NCI NIH HHS; R01 CA049797-17/CA/NCI NIH HHS; R01 CA073599-09A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bcl2l1 protein, mouse; 0/Carcinogens; 0/Proliferating Cell Nuclear Antigen; 0/Reactive Oxygen Species; 0/Transcription Factor AP-1; 0/bcl-X Protein; 1344-28-1/Aluminum Oxide; EC 1.15.1.1/Superoxide Dismutase; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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