TY - JOUR
T1 - β3-Apo-10′-carotenoids modulate placental microsomal triglyceride transfer protein expression and function to optimize transport of intact β-carotene to the embryo
AU - Costabile, Brianna K.
AU - Kim, Youn Kyung
AU - Iqbal, Jahangir
AU - Zuccaro, Michael V.
AU - Wassef, Lesley
AU - Narayanasamy, Sureshbabu
AU - Curley, Robert W.
AU - Harrison, Earl H.
AU - Hussain, M. Mahmood
AU - Quadro, Loredana
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/8/26
Y1 - 2016/8/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84984802009&partnerID=8YFLogxK
U2 - 10.1074/jbc.M116.738336
DO - 10.1074/jbc.M116.738336
M3 - Article
C2 - 27402843
AN - SCOPUS:84984802009
SN - 0021-9258
VL - 291
SP - 18525
EP - 18535
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -