Expression of cFABP and PPAR in trophoblast cells: effect of PPAR ligands on linoleic acid uptake and differentiation.
Throughout gestation, fetal growth depends, in part, on placental transfer of maternal essential fatty acid (EFA) and long-chain polyunsaturated fatty acid. All fatty acid (FA) can cross lipid bilayer by simple diffusion, such as those in the syncytiotrophoblasts, the multinucleated, terminally differentiated trophoblast cells. The trophoblasts differentiation process is accompanied by an increase of human chorionic gonadotropin (hCG) secretion and an inhibition of Human Achaete-Scute Homologue-2 expression (Hash-2). Furthermore, a number of FA-binding proteins (FABPs) have been identified in membrane and cytoplasm of mammalian cells, which are thought to facilitate the transfer of FA across membranes and their intracellular channeling. Thus, the aim of this study was to investigate the implication of cFABPs in linoleic acid (LA) uptake by human trophoblast cells according to differentiation. Moreover, since peroxisome proliferator-activated receptor (PPARs) regulate the expression of cFABP and play an important role in trophoblast cells differentiation, the effects of PPARs ligands are verified on cFABP expression and differentiation. Herein, we reported the increase of the expression of liver and heart FABP (L- and H-FABP) upon differentiation of trophoblast cells, an inhibition of PPAR alpha and beta, while PPAR gamma levels remains unchanged. The nonselective peroxisome-proliferating agents, bezafibrate and LA, impaired trophoblast differentiation, and reduced L- and H-FABP expression. Furthermore, cobalt, a chemical agent known to mimic hypoxia, inhibits trophoblast cells differentiation and diminishes H-, L-FABP and PPARs expression. Finally, both treatments show no influence on LA uptake by trophoblast cells. In conclusion, this study showed that there is no correlation between the expression of H- and L-FABP and LA uptake by trophoblast cells and that bezafibrate and LA greatly impaired trophoblast cells differentiation.
Daoud
Georges
G
Laboratoire de Physiologie materno-fonetale, Département des Sciences Biologiques, Université du Québec à Montréal, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
Simoneau
Lucie
L
Masse
André
A
Rassart
Eric
E
Lafond
Julie
J
D051792:Basic Helix-Loop-Helix Proteins; D001629:Bezafibrate / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005333:Fetus / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008024:Ligands; D019787:Linoleic Acid / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D001629:Bezafibrate; D002352:Carrier Proteins; D003035:Cobalt; D004268:DNA-Binding Proteins; D050556:Fatty Acid-Binding Proteins; D000960:Hypolipidemic Agents; D007770:L-Lactate Dehydrogenase; D008024:Ligands; D019787:Linoleic Acid; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D014157:Transcription Factors; C065501:ASCL2 protein, human; C493319:FABP1 protein, human; C018021:cobaltous chloride