title: Regulation of fatty acid binding proteins by hypoxia inducible factors 1α and 2α in the placenta: relevance to pre-eclampsia.
abstract: Pre-eclampsia is characterized by placental hypoxia and dyslipidemia. Arachidonic and docosahexanoic acids are essential maternal nutrients for fetal development. They are transported via placental trophoblast cells by membrane and cytosolic fatty acid binding proteins. Others report the expressions of these proteins which are increased in hypoxic trophoblasts. Using bioinformatics, BeWo cells, reporter assays, quantitative real-time PCR and immunoblotting we tested the hypothesis that hypoxia inducible factors 1α (HIF-1α) and/or 2α (HIF-2α) regulate the expressions of FABP1, FABP3, FABP4 and FATP2 proteins. Three hypoxia responsive elements (HRE) were identified in FABP1 which cumulatively responded strongly to HIF-1α and weakly to HIF-2α. FABP3 expression partially responded to HIF-1α. Two putative HRE were validated in FABP4 both of which responded weakly to HIF-1α and HIF-2α. FATP2 protein expression reacted positively to hypoxia. Thus, fetal essential fatty acid supply via the placenta is protected under hypoxia. It will be interesting to determine if our findings are replicated in human pre-eclamptic placenta.
authors.affiliation: Diabetes and Nutritional Sciences Division, School of Medicine, United Kingdom.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Jadoon
authors.affiliation: Department of Biochemistry, School of Biomedical and Health Sciences, King׳s College London, Franklin Wilkins Building, Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Cunningham
authors.affiliation: Diabetes and Nutritional Sciences Division, School of Medicine, United Kingdom. Electronic address: lindsay.mcdermott@kcl.ac.uk.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: McDermott
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050556:Fatty Acid-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: Fatty acid binding proteins; Hypoxia; Hypoxia-inducible factor-1 alpha; Long chain polunsatured fatty acids; Placenta; Pre-eclampsia