title: β-Apo-10'-carotenoids Modulate Placental Microsomal Triglyceride Transfer Protein Expression and Function to Optimize Transport of Intact β-Carotene to the Embryo.
abstract: β-Carotene is an important source of vitamin A for the mammalian embryo, which depends on its adequate supply to achieve proper organogenesis. In mammalian tissues, β-carotene 15,15'-oxygenase (BCO1) converts β-carotene to retinaldehyde, which is then oxidized to retinoic acid, the biologically active form of vitamin A that acts as a transcription factor ligand to regulate gene expression. β-Carotene can also be cleaved by β-carotene 9',10'-oxygenase (BCO2) to form β-apo-10'-carotenal, a precursor of retinoic acid and a transcriptional regulator per se The mammalian embryo obtains β-carotene from the maternal circulation. However, the molecular mechanisms that enable its transfer across the maternal-fetal barrier are not understood. Given that β-carotene is transported in the adult bloodstream by lipoproteins and that the placenta acquires, assembles, and secretes lipoproteins, we hypothesized that the aforementioned process requires placental lipoprotein biosynthesis. Here we show that β-carotene availability regulates transcription and activity of placental microsomal triglyceride transfer protein as well as expression of placental apolipoprotein B, two key players in lipoprotein biosynthesis. We also show that β-apo-10'-carotenal mediates the transcriptional regulation of microsomal triglyceride transfer protein via hepatic nuclear factor 4α and chicken ovalbumin upstream promoter transcription factor I/II. Our data provide the first in vivo evidence of the transcriptional regulatory activity of β-apocarotenoids and identify microsomal triglyceride transfer protein and its transcription factors as the targets of their action. This study demonstrates that β-carotene induces a feed-forward mechanism in the placenta to enhance the assimilation of β-carotene for proper embryogenesis.
authors.affiliation: From the Department of Food Science and Rutgers Center for Lipid Research and New Jersey Institute for Food Nutrition and Health, Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Brianna K
authors.initials: BK
authors.lastname: Costabile
authors.affiliation: From the Department of Food Science and Rutgers Center for Lipid Research and New Jersey Institute for Food Nutrition and Health, Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Departments of Cell Biology and Pediatrics, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York 11203, and.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: From the Department of Food Science and Rutgers Center for Lipid Research and New Jersey Institute for Food Nutrition and Health, Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Zuccaro
authors.affiliation: From the Department of Food Science and Rutgers Center for Lipid Research and New Jersey Institute for Food Nutrition and Health, Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Lesley
authors.initials: L
authors.lastname: Wassef
authors.affiliation: College of Pharmacy and Department of Human Nutrition, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Sureshbabu
authors.initials: S
authors.lastname: Narayanasamy
authors.affiliation: College of Pharmacy and.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
authors.affiliation: Department of Human Nutrition, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
authors.affiliation: Departments of Cell Biology and Pediatrics, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York 11203, and mahmood.hussain@downstate.edu.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.affiliation: From the Department of Food Science and Rutgers Center for Lipid Research and New Jersey Institute for Food Nutrition and Health, Rutgers University, New Brunswick, New Jersey 08901, quadro@aesop.rutgers.edu.
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy / Q000235:genetics / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011257:Pregnancy Proteins; C106092:microsomal triglyceride transfer protein; D019207:beta Carotene; D049308:Dioxygenases; C493359:Bco1 protein, mouse; C481678:Bco2 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
keywords: apocarotenoid; carotenoid; metabolism; placenta; retinoid; vitamin A