PPARα: A Master Regulator of Bilirubin Homeostasis
Joint Authors
Verreault, Mélanie
Rudkowska, Iwona
Vohl, Marie-Claude
Bigo, Cyril
Kaeding, Jenny
El Husseini, Diala
Barbier, Olivier
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-07-23
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Bigo, Cyril& Kaeding, Jenny& El Husseini, Diala& Rudkowska, Iwona& Verreault, Mélanie& Vohl, Marie-Claude…[et al.]. 2014. PPARα: A Master Regulator of Bilirubin Homeostasis. PPAR Research،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-1047291
Modern Language Association (MLA)
Bigo, Cyril…[et al.]. PPARα: A Master Regulator of Bilirubin Homeostasis. PPAR Research No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-1047291
American Medical Association (AMA)
Bigo, Cyril& Kaeding, Jenny& El Husseini, Diala& Rudkowska, Iwona& Verreault, Mélanie& Vohl, Marie-Claude…[et al.]. PPARα: A Master Regulator of Bilirubin Homeostasis. PPAR Research. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-1047291
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1047291