| Regulation of cardiolipin biosynthesis by fatty acid transport protein-1 IN HEK 293 cells. | |
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MedLine Citation:
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PMID: 19523918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiolipin (CL) is a major phospholipid involved in energy metabolism mammalian mitochondria and fatty acid transport protein-1 (FATP-1) is a fatty acid transport protein that may regulate the intracellular level of fatty acyl-Coenzyme A's. Since fatty acids are required for oxidative phosphorylation via mitochondrial oxidation, we examined the effect of altering FATP-1 levels on CL biosynthesis. HEK-293 mock- and FATP-1 siRNA transfected cells or mock and FATP-1 expressing cells were incubated for 24 h with 0.1 mM oleic acid bound to albumin (1:1 molar ratio) then incubated for 24 h with 0.1 mM [1,3-(3)H]glycerol and radioactivity incorporated into CL determined. FATP-1 siRNA transfected cells exhibited reduced FATP-1 mRNA and increased incorporation of [1,3-(3)H]glycerol into CL (2-fold, p<0.05) compared to controls indicating elevation in de novo CL biosynthesis. The reason for this was an increase in [1,3-(3)H]glycerol uptake and increase in activity and mRNA expression of the CL biosynthetic enzymes. In contrast, expression of FATP-1 resulted a reduction in incorporation of [1,3-(3)H]glycerol into CL (65%, p<0.05) indicating reduced CL synthesis. [1,3-(3)H]Glycerol uptake was unaltered whereas activity of cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol synthetase (CDS) and CDS-2 mRNA expression were reduced in FATP-1 expressing cells compared to control. In addition, in vitro CDS activity was reduced by exogenous addition of oleoyl-Coenzyme A. The data indicate that CL de novo biosynthesis may be regulated by FATP-1 through CDS-2 expression in HEK 293 cells. |
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Authors:
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Ryan W Mitchell; Grant M Hatch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-11 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1788 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-05 Completed Date: 2009-12-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 2015-21 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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metabolism Blotting, Western Cardiolipins / biosynthesis*, genetics Cells, Cultured Electrophoresis, Gel, Two-Dimensional Fatty Acid Transport Proteins / antagonists & inhibitors, genetics, metabolism* Fatty Acids / metabolism Gene Expression Regulation* Glycerol / metabolism Humans Kidney / cytology, embryology Mitochondria / metabolism Phospholipids / metabolism RNA, Messenger / genetics, metabolism RNA, Small Interfering / pharmacology Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Acyl Coenzyme A; 0/Cardiolipins; 0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Phospholipids; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/SLC27A1 protein, human; 56-81-5/Glycerol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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