| First Author | Costabile BK | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 35 | Pages | 18525-35 |
| PubMed ID | 27402843 | Mgi Jnum | J:236153 |
| Mgi Id | MGI:5805303 | Doi | 10.1074/jbc.M116.738336 |
| Citation | Costabile BK, et al. (2016) beta-Apo-10'-carotenoids Modulate Placental Microsomal Triglyceride Transfer Protein Expression and Function to Optimize Transport of Intact beta-Carotene to the Embryo. J Biol Chem 291(35):18525-35 |
| abstractText | beta-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, beta-carotene 15,15'-oxygenase (BCO1) converts beta-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. beta-Carotene can also be cleaved by beta-carotene 9',10'-oxygenase (BCO2) to form beta-apo-10'-carotenal, a precursor of retinoic acid and a transcriptional regulator per se The mammalian embryo obtains beta-carotene from the maternal circulation. However, the molecular mechanisms that enable its transfer across the maternal-fetal barrier are not understood. Given that beta-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 beta-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 beta-apo-10'-carotenal mediates the transcriptional regulation of microsomal triglyceride transfer protein via hepatic nuclear factor 4alpha and chicken ovalbumin upstream promoter transcription factor I/II. Our data provide the first in vivo evidence of the transcriptional regulatory activity of beta-apocarotenoids and identify microsomal triglyceride transfer protein and its transcription factors as the targets of their action. This study demonstrates that beta-carotene induces a feed-forward mechanism in the placenta to enhance the assimilation of beta-carotene for proper embryogenesis. |
