OREGON STATE UNIVERSITY
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| Title | Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells. |
| Publication Type | Journal Article |
| Year of Publication | 2002 |
| Authors | Pawar, A, Xu, J, Jerks, E, Mangelsdorf, DJ, Jump, DB |
| Journal | J Biol Chem |
| Volume | 277 |
| Issue | 42 |
| Pagination | 39243-50 |
| Date Published | 2002 Oct 18 |
| ISSN | 0021-9258 |
| Keywords | Cell Line, Cell Nucleus, Cell-Free System, Chromatography, High Pressure Liquid, DNA-Binding Proteins, Dose-Response Relationship, Drug, Fatty Acids, Fatty Acids, Unsaturated, Gene Expression Regulation, Enzymologic, Genetic Vectors, Humans, Lipid Metabolism, Liver X Receptors, Orphan Nuclear Receptors, Plasmids, Protein Binding, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Time Factors, Transcription Factors, Transfection |
| Abstract |
Fatty acids bind to and regulate the activity of peroxisome proliferator-activated (PPAR) and liver X receptors (LXR). However, the role lipid metabolism plays in the control of intracellular fatty acid ligands is poorly understood. We have identified two strains of HEK293 cells that display differences in fatty acid regulation of nuclear receptors. Using full-length and Gal4-LBD chimeric receptors in functional assays, 20:4,n6 induced PPARalpha activity approximately 2.2-fold and suppressed LXRalpha activity by 80% (ED50 approximately 25-50 microm) in HEK293-E (early passage) cells but had no effect on PPARalpha or LXRalpha receptor activity in HEK293-L (late passage) cells. LXRbeta was insensitive to fatty acid regulation in both HEK293 strains. Metabolic labeling studies using [14C]20:4,n6 (at 100 microm) indicated that the uptake of 20:4,n6 and its assimilation into triacylglycerol, diacylglycerol, and polar lipids revealed no difference between the two strains. Such treatment increased total cellular 20:4,n6 ( approximately 11-fold) and its elongation product, 22:4,n6 ( approximately 3.6-fold), within 6 h. Non-esterified 20:4,n6 and 22:4,n6 represented |
| DOI | 10.1074/jbc.M206170200 |
| Alternate Journal | J. Biol. Chem. |
| PubMed ID | 12161442 |
| Grant List | R01 DK043220 / DK / NIDDK NIH HHS / United States DK43220 / DK / NIDDK NIH HHS / United States |