| Dihydroceramide-based response to hypoxia. | |
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MedLine Citation:
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PMID: 21914808 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To understand the mechanisms of ceramide-based responses to hypoxia, we performed a mass spectrometry-based survey of ceramide species elicited by a wide range of hypoxic conditions (0.2-5% oxygen). We describe a rapid, time-dependent, marked up-regulation of dihydroceramides (DHCs) in mammalian cells and in the lungs of hypoxic rats. The increase affected all DHC species and was proportional with the depth and duration of hypoxia, ranging from 2- (1 h) to 10-fold (24 h), with complete return to normal after 1 h of reoxygenation at the expense of increased ceramides. We demonstrate that a DHC-based response to hypoxia occurs in a hypoxia-inducible factor-independent fashion and is catalyzed by the DHC desaturase (DEGS) in the de novo ceramide pathway. Both the impact of hypoxia on DHC molecular species and its inhibitory effect on cell proliferation were reproduced by knockdown of DEGS1 or DEGS2 by siRNA during normoxia. Conversely, overexpression of DEGS1 or DEGS2 attenuated the DHC accumulation and increased cell proliferation during hypoxia. Based on the amplitude and kinetics of DHC accumulation, the enzymatic desaturation of DHCs fulfills the criteria of an oxygen sensor across physiological hypoxic conditions, regulating the balance between biologically active components of ceramide metabolism. |
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Authors:
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Cecilia M Devlin; Tim Lahm; Walter C Hubbard; Mary Van Demark; Kevin C Wang; Xue Wu; Alicja Bielawska; Lina M Obeid; Mircea Ivan; Irina Petrache |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-09-13 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-31 Completed Date: 2012-01-09 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38069-78 Citation Subset: IM |
Affiliation:
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Department of Medicine, Indiana University, Indianapolis, Indiana 46202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia* Biosensing Techniques Cell Line, Tumor Cell Proliferation Ceramides / chemistry, pharmacology* Dose-Response Relationship, Drug Humans Kinetics Male Mass Spectrometry / methods Mice Oxidoreductases / chemistry* Oxygen / chemistry RNA, Small Interfering / metabolism Rats Rats, Sprague-Dawley Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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1S10RR16798/RR/NCRR NIH HHS; R01HL077328/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ceramides; 0/RNA, Small Interfering; 0/dihydroceramide; 7782-44-7/Oxygen; EC 1.-/Oxidoreductases; EC 1.3.1.-/dihydroceramide desaturase |
| Comments/Corrections | |
Erratum In:
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J Biol Chem. 2012 May 18;287(21):17425 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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