| Hyperoxia augments ER-stress-induced cell death independent of BiP loss. | |
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MedLine Citation:
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PMID: 19786088 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytotoxic reactive oxygen species are constantly formed as a by-product of aerobic respiration and are thought to contribute to aging and disease. Cells respond to oxidative stress by activating various pathways, whose balance is important for adaptation or induction of cell death. Our lab recently reported that BiP (GRP78), a proposed negative regulator of the unfolded protein response (UPR), declines during hyperoxia, a model of chronic oxidative stress. Here, we investigate whether exposure to hyperoxia, and consequent loss of BiP, activates the UPR or sensitizes cells to ER stress. Evidence is provided that hyperoxia does not activate the three ER stress receptors IRE1, PERK, and ATF6. Although hyperoxia alone did not activate the UPR, it sensitized cells to tunicamycin-induced cell death. Conversely, overexpression of BiP did not block hyperoxia-induced ROS production or increased sensitivity to tunicamycin. These findings demonstrate that hyperoxia and loss of BiP alone are insufficient to activate the UPR. However, hyperoxia can sensitize cells to toxicity from unfolded proteins, implying that chronic ROS, such as that seen throughout aging, could augment the UPR and, moreover, suggesting that the therapeutic use of hyperoxia may be detrimental for lung diseases associated with ER stress. |
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Authors:
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Jennifer S Gewandter; Rhonda J Staversky; Michael A O'Reilly |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-09-26 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 47 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-16 Completed Date: 2010-01-26 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 1742-52 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Biophysics, The University of Rochester, Rochester, NY 14642, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Cell Line, Tumor Endoplasmic Reticulum / drug effects, metabolism* Heat-Shock Proteins / genetics, metabolism* Humans Mice Mice, Inbred C57BL Oxidative Stress* Oxygen / metabolism*, pharmacology Protein Folding Reactive Oxygen Species / metabolism Stress, Physiological* |
| Grant Support | |
ID/Acronym/Agency:
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ES-01247/ES/NIEHS NIH HHS; HL-66988/HL/NHLBI NIH HHS; HL-67392/HL/NHLBI NIH HHS; P30 ES001247-359022/ES/NIEHS NIH HHS; R01 HL067392-07/HL/NHLBI NIH HHS; T32 HL066988-09/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Heat-Shock Proteins; 0/Reactive Oxygen Species; 0/molecular chaperone GRP78; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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