Journal
LIFE SCIENCES
Volume 80, Issue 2, Pages 140-145Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2006.08.029
Keywords
PPAR alpha; polyunsaturated fatty acid; chimera reporter assay; Caco-2
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It is thought that peroxisome proliferator-activated receptor alpha (PPAR alpha) is a major regulator for fatty acid metabolism. Long-chain fatty acids have been shown to induce expression of the genes related to fatty acid metabolism through PPAR alpha. However, it is unclear whether the intensity of PPAR alpha activation is different among various fatty acids. In this study, we compared various fatty acids in the capability of PPAR alpha activation by differential protease sensitivity assay (DPSA), electrophoretic mobility shift assay and GAL4-PPAR chimera reporter assay in intestinal cell line, Caco-2. DPSA revealed that polyunsaturated fatty acids of 18 to 20 carbon groups with 3-5 double bonds strongly induced a PPAR alpha conformational change. The ligand-induced changes in the sensitivity to protease corresponded to the enhancement of the binding of PPAR alpha-RXR alpha heterodimer to the PPAR-response element (PPRE). The GAL4-PPAR chimera reporter assay revealed that the DNA binding-independent transactivity of PPAR alpha was induced by various fatty acids with a wide spectrum of intensity which correlated with the conformational change of PPAR alpha. These results suggest that PPAR alpha has greater selectivity to certain types of polyunsaturated fatty acids, and that the ligand-induced conformational change of PPAR alpha leads to parallel increases in both DNA binding to the PPAR-response element and the DNA binding-independent transactivity. (c) 2006 Elsevier Inc. All rights reserved.
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