The formation, occurrence, and function of β-apocarotenoids: β-carotene metabolites that may modulate nuclear receptor signaling.
β-Carotene is the major dietary source of provitamin A. Central cleavage of β-carotene yields 2 molecules of retinal followed by further oxidation to retinoic acid. Eccentric cleavage of β-carotene occurs at double bonds other than the central double bond, and the products of these reactions are β-apocarotenals and β-apocarotenones. We reviewed recent developments in 3 areas: 1): the enzymatic production of β-apocarotenoids in higher animals; 2) the occurrence of β-apocarotenoids in foods and animal tissues; and 3) the biological activity of β-apocarotenoids, particularly on retinoid receptors. HPLC-mass spectrometry techniques were developed to quantify these compounds in mouse serum and tissues and in foods. β-Apo-10'- and -12'-carotenals were detected in mouse serum and liver. β-Apo-8'-, β-apo-10'-, β-apo-12'-, and β-apo-14'-carotenals and β-apo-13-carotenone were detected in orange-fleshed melons. Transactivation assays were performed to see whether apocarotenoids activate or antagonize retinoid X receptor (RXR) α. Reporter gene constructs and retinoid receptor (RXRα) were transfected into cells, which were used to perform quantitative assays for the activation of this ligand-dependent transcription factor. None of the β-apocarotenoids significantly activated RXRα. However, β-apo-13-carotenone antagonized the 9-cis-retinoic acid activation of RXRα. Competitive radioligand binding assays showed that this antagonist competes directly with the agonist for binding to purified receptor, a finding confirmed by molecular modeling studies. These findings suggest that a possible biological function of β-apocarotenoids is their ability to interfere with nuclear receptor signaling. Recent work showed that β-apo-13-carotenone is also a high-affinity antagonist of all 3 retinoic acid receptors (RARα, RARβ, and RARγ).
Department of Human Nutrition and Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, 43210, USA. harrison.304@osu.edu
Earl H
EH
Harrison
Carlo
C
dela Sena
Abdulkerim
A
Eroglu
Matthew K
MK
Fleshman
D000818:Animals; D002338:Carotenoids / Q000378:metabolism*; D005502:Food; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D019207:beta Carotene; D002338:Carotenoids; D014212:Tretinoin; C004984:apocarotenal