| Reduction in cholesterol synthesis in response to serum starvation in lymphoblasts of a patient with Barth syndrome. | |
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MedLine Citation:
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PMID: 20651830 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Barth syndrome is a rare X-linked disease in which mild hypocholesterolemia is observed in some patients. We investigated cholesterol biosynthesis in lymphoblasts from a normal and age-matched Barth syndrome patient. Control and Barth syndrome (DeltaTAZ1) lymphoblasts were incubated in the presence or absence of serum to induce cholesterol synthesis and hydroxymethylglutaryl-coenzyme A reductase activity and expression, and cholesterol biosynthesis from radioactive precursors was determined. Cholesterol biosynthesis from [2-14C]pyruvate was stimulated 2-fold in control cells, but was unchanged in DeltaTAZ1 lymphoblasts, and from [1-14C]acetate was stimulated 77% in control but only 26% in DeltaTAZ1 lymphoblasts upon serum removal, indicating a lower ability of DeltaTAZ1 cells to upregulate cholesterol biosynthesis. The reason was an inability to increase hydroxymethylglutaryl-coenzyme A reductase activity, which was already near maximum in DeltaTAZ1 lymphoblasts, in response to serum removal, compared with control cells. The reduced ability to increase hydroxymethylglutaryl-coenzyme A reductase enzyme activity in DeltaTAZ1 lymphoblasts was due to a decrease in hydroxymethylglutaryl-coenzyme A reductase messenger RNA. Although total cholesterol levels are similar under standard culture conditions, DeltaTAZ1 lymphoblasts have a diminished capacity to respond to increased demand for cholesterol biosynthesis because of an already elevated level of synthesis under standard culture conditions. |
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Authors:
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Kristin D Hauff; Grant M Hatch |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemistry and cell biology = Biochimie et biologie cellulaire Volume: 88 ISSN: 1208-6002 ISO Abbreviation: Biochem. Cell Biol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-23 Completed Date: 2010-12-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8606068 Medline TA: Biochem Cell Biol Country: Canada |
Other Details:
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Languages: eng Pagination: 595-602 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, Center on Aging, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
metabolism Acetic Acid / pharmacokinetics Barth Syndrome / genetics, metabolism, pathology* Carbon Radioisotopes / pharmacokinetics Cells, Cultured Cholesterol / biosynthesis* Culture Media, Serum-Free / pharmacology* Gene Deletion Gene Expression Regulation / drug effects Humans Hydroxymethylglutaryl CoA Reductases / genetics, metabolism Lymphocytes / drug effects*, metabolism, pathology* Pyruvic Acid / pharmacokinetics Receptors, LDL / genetics, metabolism Starvation / metabolism Transcription Factors / genetics |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Carbon Radioisotopes; 0/Culture Media, Serum-Free; 0/Receptors, LDL; 0/TAZ protein, human; 0/Transcription Factors; 127-17-3/Pyruvic Acid; 57-88-5/Cholesterol; 64-19-7/Acetic Acid; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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