碩士 / 國立陽明大學 / 生物化學研究所 / 93 / Abstract
The effect of polyunsaturated fatty acids (PUFAs) on the development of atherosclerosis has been investigated in our previous study by using apo E knockout mice as the animal model. However, the mechanism contributing to the role of n-3 PUFAs in atherosclerosis has not been fully understood. The aim of this study was to investigate the regulation mechanism of PUFAs in peroxisome proliferator-activated receptors (PPARs)-mediated cholesterol efflux pathway. We have hypothesized that some PUFAs may exert anti-atherosclerotic effects through PPARs activation and the ATP-binding cassette transporter A1 (ABCA1) pathway. Our study showed that treatment of 80 mM PUFAs and 5 mM 9-cis-retinoic acid (9-cis-RA), the ligand for the retinoic acid X receptor (RXR), enhanced cholesterol efflux remarkably in RAW 264.7 cells. Combination of PUFAs and 9-cis-RA also increased liver X receptor α (LXRα) and ABCA1 gene expression in the RAW 264.7 cells. We also investigated the PUFA-mediated activation of PPARs by luciferase assay. HeLa cells were co-transfected with PPAR-responsive elements (PPRE)-tk-luciferase reporter plasmid and PPAR expression vectors, followed by PUFAs and 9-cis-RA incubation. The promoter activity of LXRα was transactivated by docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or linoleic acid (LA) in combination with 9-cis-RA. Finally, we investigated the effects of PUFAs on binding of PPARs to the PPREs by an electrophoretic mobility shift assay (EMSA). It revealed that combination of PUFAs and 9-cis-RA increased PPARγ binding activity. Taken together, it appears that administration of PUFAs and RXR agonists increase cholesterol efflux through the PPARγ-LXRα-ABCA1 pathway and this may benefit to the regression of atherosclerosis.
| Identifer | oai:union.ndltd.org:TW/093YM005107013 |
| Date | January 2005 |
| Creators | Pei-Chin Tsai, 蔡佩秦 |
| Contributors | An-Na Chiang, 姜安娜 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 84 |
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