| Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T schwannoma cells. | |
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MedLine Citation:
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PMID: 19171550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly expressed in myelin-forming cells of the nervous system and in epidermal keratinocytes. While hFA-sphingolipids are thought to enhance the physical stability of specialized membranes produced by these cells, physiological significance of hFA-sphingolipids in many other cell types is unknown. In this study, we report novel roles for FA2H and hFA-sphingolipids in the regulation of the cell cycle. Treatment of D6P2T Schwannoma cells with dibutyryl-cAMP (db-cAMP) induced exit from the cell cycle with concomitant upregulation of FA2H. Partial silencing of FA2H in D6P2T cells resulted in 60-70% reduction of hFA-dihydroceramide and hFA-ceramide, with no effect on nonhydroxy dihydroceramide and ceramide. Under these conditions, db-cAMP no longer induced cell cycle exit, and cells continued to grow and divide. Immunoblot analyses revealed that FA2H silencing prevented db-cAMP-induced upregulation of cyclin-dependent kinase inhibitors p21 and p27. These results provide evidence that FA2H is a negative regulator of the cell cycle and facilitates db-cAMP-induced cell cycle exit in D6P2T cells. |
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Authors:
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Nathan L Alderson; Hiroko Hama |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-01-22 |
Journal Detail:
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Title: Journal of lipid research Volume: 50 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-18 Completed Date: 2009-08-12 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1203-8 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bucladesine / pharmacology* Cell Cycle / drug effects*, physiology* Cell Line, Tumor Ceramides / metabolism Fatty Acids / metabolism Gene Silencing Mixed Function Oxygenases / antagonists & inhibitors, genetics, metabolism* Neurilemmoma / enzymology*, pathology* RNA, Small Interfering / genetics Rats Sphingolipids / metabolism Up-Regulation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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NS-060807/NS/NINDS NIH HHS; RR-17677/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ceramides; 0/Fatty Acids; 0/RNA, Small Interfering; 0/Sphingolipids; 362-74-3/Bucladesine; EC 1.-/Mixed Function Oxygenases; EC 1.-/fatty acid alpha-hydroxylase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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