An official website of the United States government
Development of a nutritious, sustainable food source is essential to address worldwide deficiencies in human micronutrients. Aquatic floating plants (e.g., species in the family Lemnaceae, duckweeds) are uniquely suited for area-efficient productivity with exceptionally high rates of growth and nutritional quality. Here, we provide an overview of the role of dietary micronutrients (with a focus on carotenoids) in human health and the promise of Lemnaceae as sustainable crops. We examine the effect of growth light environment on plant biomass production and levels of the carotenoids zeaxanthin, lutein, and pro-vitamin A (β-carotene), as well as the antioxidant vitamin E (α-tocopherol), and protein. Data on each of these nutrients are reported on a plant dry biomass basis (as relevant for nutrition) as well as relative to the required input of light energy (as relevant to resource-use efficiency).
more »
« less
Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2
An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of β-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer’s disease symptoms. Mammalian β-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as β-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with β-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation.
more »
« less
- Award ID(s):
- 1709921
- PAR ID:
- 10217328
- Date Published:
- Journal Name:
- Antioxidants
- Volume:
- 10
- Issue:
- 3
- ISSN:
- 2076-3921
- Page Range / eLocation ID:
- 413
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Tools for tuning transcription in mammalian cells have broad applications, from basic biological discovery to human gene therapy. While precise control over target gene transcription via dosing with small molecules (drugs) is highly sought, the design of such inducible systems that meets required performance metrics poses a great challenge in mammalian cell synthetic biology. Important characteristics include tight and tunable gene expression with a low background, minimal drug toxicity, and orthogonality. Here, we review small-molecule-inducible transcriptional control devices that have demonstrated success in mammalian cells and mouse models. Most of these systems employ natural or designed ligand-binding protein domains to directly or indirectly communicate with transcription machinery at a target sequence, via carefully constructed fusions. Example fusions include those to transcription activator-like effectors (TALEs), DNA-targeting proteins (e.g. dCas systems) fused to transactivating domains, and recombinases. Similar to the architecture of Type I nuclear receptors, many of the systems are designed such that the transcriptional controller is excluded from the nucleus in the absence of an inducer. Techniques that use ligand-induced proteolysis and antibody-based chemically induced dimerizers are also described. Collectively, these transcriptional control devices take advantage of a variety of recently developed molecular biology tools and cell biology insights and represent both proof of concept (e.g. targeting reporter gene expression) and disease-targeting studies.more » « less
-
Cellulose nanocrystals (CNCs) have great potential in many areas of research, applications, and future commercialization prospects. Recently, CNCs have emerged as attractive candidates for biomedical applications such as drug and gene delivery systems. As such, cytotoxicity studies have been the major focus in the past decade. However, despite the rod-like nature of CNCs, the potential immune response of surface-modified CNCs is not well investigated. The current study examined the potential immune and antioxidant response induced by CNCs grafted with β -cyclodextrin (CNCs- β -CD) in a human monocyte cell line (THP-1) and a mouse macrophage-like cell line (J774A.1). We analyzed the secretion of the proinflammatory cytokine, interleukin 1 β (IL-1 β ), by ELISA and mitochondria-derived reactive oxygen species (ROS) using fluorescence cell imaging and examined the intracellular levels of proteins involved in the immune and antioxidant response by immunoblotting. Our results indicated a dramatic increase neither in the IL-1 β secretion nor in the mitochondria-derived ROS resulting in no changes in the intracellular antioxidant response in THP-1 cells treated with different concentrations of CNCs- β -CD. Overall, CNCs- β -CD is nonimmunogenic and do not induce an increased antioxidant response under the conditions tested and hence has the potential to be used as a drug delivery carrier.more » « less
-
Abstract Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens inC. elegansto discover a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. DeletingC. elegansERGU-1 causes excessive H2O2and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behavioral responses to H2O2. BothC. elegansand human ERGU-1 proteins localize to ER membranes and form network reticulum structures. Human andDrosophilahomologs of ERGU-1 can rescueC. elegansmutant phenotypes, demonstrating evolutionarily ancient and conserved functions. In addition, purified ERGU-1 and human homolog TMEM161B exhibit redox-modulated oligomeric states. Together, our results reveal an ER-membrane-specific protein machinery for peroxide detoxification and suggest a previously unknown and conserved mechanisms for antioxidant defense in animal cells.more » « less
-
ABSTRACT miR-31 is a highly conserved microRNA that plays crucial roles in cell proliferation, migration and differentiation. We discovered that miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeletal and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, including β-actin, Gelsolin, Rab35 and Fascin. De novo translation of Fascin occurs at the mitotic spindle of sea urchin embryos and mammalian cells. Importantly, miR-31 inhibition leads to a significant a increase of newly translated Fascin at the spindle of dividing sea urchin embryos. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, highlighting the importance of the regulation of local translation by miR-31 at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/antiox10030413
