title: Actions of β-apo-carotenoids in differentiating cells: differential effects in P19 cells and 3T3-L1 adipocytes.
abstract: β-Apo-carotenoids, including β-apo-13-carotenone and β-apo-14'-carotenal, are potent retinoic acid receptor (RAR) antagonists in transactivation assays. We asked how these influence RAR-dependent processes in living cells. Initially, we explored the effects of β-apo-13-carotenone and β-apo-14'-carotenal on P19 cells, a mouse embryonal carcinoma cell line that differentiates into neurons when treated with all-trans-retinoic acid. Treatment of P19 cells with either compound failed to block all-trans-retinoic acid induced differentiation. Liquid chromatography tandem mass spectrometry studies, however, established that neither of these β-apo-carotenoids accumulates in P19 cells. All-trans-retinoic acid accumulated to high levels in P19 cells. This suggests that the uptake and metabolism of β-apo-carotenoids by some cells does not involve the same processes used for retinoids and that these may be cell type specific. We also investigated the effects of two β-apo-carotenoids on 3T3-L1 adipocyte marker gene expression during adipocyte differentiation. Treatment of 3T3-L1 adipocytes with either β-apo-13-carotenone or β-apo-10'-carotenoic acid, which lacks RAR antagonist activity, stimulated adipocyte marker gene expression. Neither blocked the inhibitory effects of a relatively large dose of exogenous all-trans-retinoic acid on adipocyte differentiation. Our data suggest that in addition to acting as transcriptional antagonists, some β-apo-carotenoids act through other mechanisms to influence 3T3-L1 adipocyte differentiation.
authors.affiliation: Columbia College, Columbia University, New York, NY 10032, United States.
authors.forename: Cynthia X
authors.initials: CX
authors.lastname: Wang
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Yuen
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, United States.
authors.forename: Sureshbabu
authors.initials: S
authors.lastname: Narayanasamy
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
authors.affiliation: Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, United States.
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States. Electronic address: wsb2@columbia.edu.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects*; D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018168:Receptors, Retinoic Acid; D002338:Carotenoids; D014212:Tretinoin; C071311:beta-apo-14'-carotenal; C071310:beta-apo-13-carotenone
keywords: Adipose differentiation; All-trans-retinoic acid; Gene expression; Obesity; Retinoid; Transcription