ArticleThe Journal of biological chemistry2012
Naturally occurring eccentric cleavage products of provitamin A β-carotene function as antagonists of retinoic acid receptors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 132 citations in OpenAlex.
- The effect of β-carotene on the mortality of male smokers is modified by smoking and by vitamins C and E: evidence against a uniform effect of nutrient.Journal of nutritional science · 2020Trial
- Limited appearance of apocarotenoids is observed in plasma after consumption of tomato juices: a randomized human clinical trial.The American journal of clinical nutrition · 2018Trial
- Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.Journal of the neurological sciences · 2017Trial
- Lycopene, Carotenoids, and Retinoids in Cancer Chemoprevention: Molecular Mechanisms and Clinical Implications.Nutrients · 2026Review
- The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Patterns and Determinants of Micronutrient Dietary Biomarkers and Their Associations with Dietary Intakes in Young Children.The Journal of nutrition · 2024Article
- Pigments from pathogenic bacteria: a comprehensive update on recent advances.World journal of microbiology & biotechnology · 2024Review
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
- Carotenoids and Their Health Benefits as Derived via Their Interactions with Gut Microbiota.Advances in nutrition (Bethesda, Md.) · 2023Review
- Article
- Review
- Carotenoids in orange carrots mitigate non-alcoholic fatty liver disease progression.Frontiers in nutrition · 2022Article
- The Structural and Biochemical Basis of Apocarotenoid Processing by β-Carotene Oxygenase-2.ACS chemical biology · 2021Article
- Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2.Antioxidants (Basel, Switzerland) · 2021Article
- The Role of β-Carotene in Colonic Inflammation and Intestinal Barrier Integrity.Frontiers in nutrition · 2021Article
- Molecular components affecting ocular carotenoid and retinoid homeostasis.Progress in retinal and eye research · 2021Review
- Carotenoid metabolism at the intestinal barrier.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Interplay between β-carotene and lipoprotein metabolism at the maternal-fetal barrier.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Effect of nano-encapsulation of β-carotene onToxicology reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
β-Carotene is the major dietary source of provitamin A. Central cleavage of β-carotene catalyzed by β-carotene oxygenase 1 yields two molecules of retinaldehyde. Subsequent oxidation produces all-trans-retinoic acid (ATRA), which functions as a ligand for a family of nuclear transcription factors, the retinoic acid receptors (RARs). Eccentric cleavage of β-carotene at non-central double bonds is catalyzed by other enzymes and can also occur non-enzymatically. The products of these reactions are β-apocarotenals and β-apocarotenones, whose biological functions in mammals are unknown. We used reporter gene assays to show that none of the β-apocarotenoids significantly activated RARs. Importantly, however, β-apo-14'-carotenal, β-apo-14'-carotenoic acid, and β-apo-13-carotenone antagonized ATRA-induced transactivation of RARs. Competitive radioligand binding assays demonstrated that these putative RAR antagonists compete directly with retinoic acid for high affinity binding to purified receptors. Molecular modeling studies confirmed that β-apo-13-carotenone can interact directly with the ligand binding site of the retinoid receptors. β-Apo-13-carotenone and the β-apo-14'-carotenoids inhibited ATRA-induced expression of retinoid responsive genes in Hep G2 cells. Finally, we developed an LC/MS method and found 3-5 nm β-apo-13-carotenone was present in human plasma. These findings suggest that β-apocarotenoids function as naturally occurring retinoid antagonists. The antagonism of retinoid signaling by these metabolites may have implications for the activities of dietary β-carotene as a provitamin A and as a modulator of risk for cardiovascular disease and cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.