PPARα: A Master Regulator of Bilirubin Homeostasis
Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical v...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2014/747014 |
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| author | Cyril Bigo Jenny Kaeding Diala El Husseini Iwona Rudkowska Mélanie Verreault Marie Claude Vohl Olivier Barbier |
| author_facet | Cyril Bigo Jenny Kaeding Diala El Husseini Iwona Rudkowska Mélanie Verreault Marie Claude Vohl Olivier Barbier |
| author_sort | Cyril Bigo |
| collection | DOAJ |
| description | Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed. |
| format | Article |
| id | doaj-art-295c03c543574e68b17941fba74c1349 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-295c03c543574e68b17941fba74c13492025-02-03T01:04:46ZengWileyPPAR Research1687-47571687-47652014-01-01201410.1155/2014/747014747014PPARα: A Master Regulator of Bilirubin HomeostasisCyril Bigo0Jenny Kaeding1Diala El Husseini2Iwona Rudkowska3Mélanie Verreault4Marie Claude Vohl5Olivier Barbier6Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, G1V 4G2, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, G1V 4G2, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, G1V 4G2, CanadaEndocrinology and Nephrology, CHU de Québec Research Center, Québec, QC, G1V 4G2, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, G1V 4G2, CanadaInstitute of Nutraceuticals and Functional Foods (INAF), Laval University, Québec, QC, G1V 0A6, CanadaLaboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, G1V 4G2, CanadaHypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed.http://dx.doi.org/10.1155/2014/747014 |
| spellingShingle | Cyril Bigo Jenny Kaeding Diala El Husseini Iwona Rudkowska Mélanie Verreault Marie Claude Vohl Olivier Barbier PPARα: A Master Regulator of Bilirubin Homeostasis PPAR Research |
| title | PPARα: A Master Regulator of Bilirubin Homeostasis |
| title_full | PPARα: A Master Regulator of Bilirubin Homeostasis |
| title_fullStr | PPARα: A Master Regulator of Bilirubin Homeostasis |
| title_full_unstemmed | PPARα: A Master Regulator of Bilirubin Homeostasis |
| title_short | PPARα: A Master Regulator of Bilirubin Homeostasis |
| title_sort | pparα a master regulator of bilirubin homeostasis |
| url | http://dx.doi.org/10.1155/2014/747014 |
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