| Decrease in membrane phospholipid unsaturation induces unfolded protein response. | |
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MedLine Citation:
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PMID: 20489212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR. |
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Authors:
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Hiroyuki Ariyama; Nozomu Kono; Shinji Matsuda; Takao Inoue; Hiroyuki Arai |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-20 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-08-06 Revised Date: 2010-10-07 |
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: 22027-35 Citation Subset: IM |
Affiliation:
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Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Acylglycerophosphocholine O-Acyltransferase
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deficiency,
metabolism Cell Death / drug effects Cell Membrane / drug effects, metabolism* Fatty Acids, Unsaturated / metabolism* Gene Knockdown Techniques Hela Cells Humans Palmitic Acid / pharmacology, toxicity Phospholipids / chemistry* Stearoyl-CoA Desaturase / deficiency, metabolism Unfolded Protein Response* / drug effects Up-Regulation / drug effects eIF-2 Kinase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Unsaturated; 0/Phospholipids; 57-10-3/Palmitic Acid; EC 1.14.19.1/Stearoyl-CoA Desaturase; EC 2.3.1.23/1-Acylglycerophosphocholine O-Acyltransferase; EC 2.3.1.23/LPCAT3 protein, human; EC 2.7.10.-/PERK kinase; EC 2.7.11.1/eIF-2 Kinase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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