| pubmed-article:10799518 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0085080 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0038323 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0531370 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C1158423 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0220905 | lld:lifeskim |
| pubmed-article:10799518 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:10799518 | pubmed:issue | 19 | lld:pubmed |
| pubmed-article:10799518 | pubmed:dateCreated | 2000-6-8 | lld:pubmed |
| pubmed-article:10799518 | 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. | lld:pubmed |
| pubmed-article:10799518 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10799518 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10799518 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:10799518 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10799518 | pubmed:month | May | lld:pubmed |
| pubmed-article:10799518 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:10799518 | pubmed:author | pubmed-author:RidgwayN DND | lld:pubmed |
| pubmed-article:10799518 | pubmed:author | pubmed-author:LagaceT ATA | lld:pubmed |
| pubmed-article:10799518 | pubmed:author | pubmed-author:StoreyM KMK | lld:pubmed |
| pubmed-article:10799518 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10799518 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:10799518 | pubmed:volume | 275 | lld:pubmed |
| pubmed-article:10799518 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10799518 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10799518 | pubmed:pagination | 14367-74 | lld:pubmed |
| pubmed-article:10799518 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:10799518 | pubmed:meshHeading | pubmed-meshheading:10799518... | lld:pubmed |
| pubmed-article:10799518 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:10799518 | pubmed:articleTitle | Regulation of phosphatidylcholine metabolism in Chinese hamster ovary cells by the sterol regulatory element-binding protein (SREBP)/SREBP cleavage-activating protein pathway. | lld:pubmed |
| pubmed-article:10799518 | pubmed:affiliation | Atlantic Research Center and the Departments of Pediatrics and Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada. | lld:pubmed |
| pubmed-article:10799518 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10799518 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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