10799518

Source:http://linkedlifedata.com/resource/pubmed/id/10799518

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0033684, umls-concept:C0038323, umls-concept:C0085080, umls-concept:C0220905, umls-concept:C0531370, umls-concept:C0851285, umls-concept:C1158423, umls-concept:C1704259, umls-concept:C1705987
pubmed:issue	19
pubmed:dateCreated	2000-6-8
pubmed:abstractText	Sterol regulation-defective (SRD) 4 cells expressing a mutant sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP D443N) and Chinese hamster ovary (CHO) cells stably expressing SCAP (CHO-SCAP) and SCAP D443N (CHO-SCAP-D443N) have increased cholesterol and fatty acid synthesis because of constitutive processing of SREBPs. We assessed whether constitutive activation of SREBPs also influenced the CDP-choline pathway for phosphatidylcholine (PtdCho) biosynthesis. Relative to control CHO 7 cells, SRD 4 cells displayed increased PtdCho synthesis and degradation as indicated by a 4-6-fold increase in [(3)H]choline incorporation into PtdCho and 10-15-fold increase in intracellular [(3)H]glycerophosphocholine. [(3)H]Phosphocholine levels in SRD 4 cells were reduced by over 10-fold, suggesting enhanced activity of CTP:phosphocholine cytidylyltransferase alpha (CCTalpha). CHO-SCAP and CHO-SCAP D443N cells displayed modest increases in [(3)H]choline incorporation into PtdCho (2-fold) and only a 2-fold reduction in [(3)H]phosphocholine. Elevated PtdCho metabolism in SRD 4, compared with SCAP-overexpressing cells, was correlated with fatty acid synthesis. Inhibition of fatty acid synthesis by cerulenin resulted in almost complete normalization of PtdCho synthesis and choline metabolite profiles in SRD 4 cells, indicating that fatty acids or a fatty acid-derived metabolite was responsible for up-regulation of PtdCho synthesis. In contrast to apparent activation in vivo, CCTalpha protein, mRNA, and in vitro activity were reduced in SRD 4 cells and unchanged in SCAP transfected cells. Unlike control and SCAP transfected cells, CCTalpha in SRD 4 cells was localized by immunofluorescence to the nuclear envelope, suggesting that residual enzyme activity in these cells was in an active membrane-associated form. Translocation of CCTalpha to the nuclear envelope was reproduced by treatment of CHO 7 cells with exogenous oleate. We conclude that the SREBP/SCAP pathway regulates PtdCho synthesis via post-transcriptional activation of nuclear CCTalpha by fatty acids or a fatty acid-derived signal.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985121R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Choline-Phosphate..., http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Diacylglycerol..., http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/SREBP cleavage-activating protein, http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding..., http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	0021-9258
pubmed:author	pubmed-author:LagaceT ATA, pubmed-author:RidgwayN DND, pubmed-author:StoreyM KMK
pubmed:issnType	Print
pubmed:day	12
pubmed:volume	275
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	14367-74
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:10799518-Animals, pubmed-meshheading:10799518-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:10799518-CHO Cells, pubmed-meshheading:10799518-Choline-Phosphate Cytidylyltransferase, pubmed-meshheading:10799518-Cricetinae, pubmed-meshheading:10799518-Cricetulus, pubmed-meshheading:10799518-DNA-Binding Proteins, pubmed-meshheading:10799518-Diacylglycerol Cholinephosphotransferase, pubmed-meshheading:10799518-HeLa Cells, pubmed-meshheading:10799518-Humans, pubmed-meshheading:10799518-Hydrolysis, pubmed-meshheading:10799518-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:10799518-Membrane Proteins, pubmed-meshheading:10799518-Nuclear Proteins, pubmed-meshheading:10799518-Phosphatidylcholines, pubmed-meshheading:10799518-RNA, Messenger, pubmed-meshheading:10799518-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:10799518-Transcription Factors, pubmed-meshheading:10799518-Transfection
pubmed:year	2000
pubmed:articleTitle	Regulation of phosphatidylcholine metabolism in Chinese hamster ovary cells by the sterol regulatory element-binding protein (SREBP)/SREBP cleavage-activating protein pathway.
pubmed:affiliation	Atlantic Research Center and the Departments of Pediatrics and Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't