Browsing by Subject "α-tocopherol"

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    Asthma, Allergy and Vitamin E: Current and Future Perspectives
    (Elsevier, 2022) Cook-Mills, Joan M.; Averill, Samantha H.; Lajiness, Jacquelyn D.; Pediatrics, School of Medicine
    Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.
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    b-Glucosylceramides and Tocopherols Regulate Development and Function of Dendritic Cells
    (American Association of Immunologists, 2022-11-15) Lajiness, Jacquelyn D.; Amarsaikhan, Nansalmaa; Tat, Kiet; Tsoggerel, Angar; Cook-Mills, Joan M.; Microbiology and Immunology, School of Medicine
    In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers) that are transported to the fetus via the placenta and to offspring via milk. The elevated βGlcCers increase numbers of fetal liver CD11c+CD11b+ dendritic cells (DCs) and offspring allergen-induced lung eosinophilia. These effects are modifiable by maternal dietary supplementation with the plant-derived lipids α-tocopherol and γ-tocopherol. It is not known whether βGlcCers and tocopherols directly regulate development of DCs. In this study, we demonstrated that βGlcCers increased development of GM-CSF-stimulated mouse bone marrow-derived DCs (BMDCs) in vitro without altering expression of costimulatory molecules. This increase in BMDC numbers was blocked by α-tocopherol and potentiated by γ-tocopherol. Furthermore, βGlcCers increased PKCα and PKCδ activation in BMDCs that was blocked by α-tocopherol. In contrast, γ-tocopherol increased BMDC PKCα and PKCδ activation and enhanced the βGlcCer-induced increase in PKCδ activation in a DC subset. Antigen processing per DC was minimally enhanced in βGlcCer-treated BMDCs and not altered ex vivo in lung DCs from pups of allergic mothers. Pups of allergic mothers had an increased proportion of CD11b+CD11c+ subsets of DCs, contributing to enhanced stimulation of T cell proliferation ex vivo. Thus, βGlcCer, which is both necessary and sufficient for development of allergic predisposition in offspring of allergic mothers, directly increased development and PKC activation in BMDCs. Furthermore, this was modifiable by dietary tocopherols. This may inform design of future studies for the prevention or intervention in asthma and allergic disease.
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    Vitamin E - phosphatidylethanolamine interactions in mixed membranes with sphingomyelin: Studies by 2H NMR
    (Elsevier, 2020-09) Cavazos, Andres T.; Kinnun, Jacob J.; Williams, Justin A.; Wassall, Stephen R.; Chemistry and Chemical Biology, School of Science
    Among the structurally diverse collection of lipids that comprise the membrane lipidome, polyunsaturated phospholipids are particularly vulnerable to oxidation. The role of α-tocopherol (vitamin E) is to protect this influential class of membrane phospholipid from oxidative damage. Whether lipid-lipid interactions play a role in supporting this function is an unanswered question. Here, we compare the molecular organization of polyunsaturated 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylethanolamine (PDPE-d31) and, as a control, monounsaturated 1-[2H31]palmitoyl-2-oleoylphosphatidylethanolamine (POPE-d31) mixed with sphingomyelin (SM) and α-tocopherol (α-toc) (2:2:1 mol) by solid-state 2H NMR spectroscopy. In both cases the effect of α-toc appears similar. Spectral moments reveal that the main chain melting transition of POPE-d31 and PDPE-d31 is broadened beyond detection. A spectral component attributed to the formation of inverted hexagonal HII phase in coexistence with lamellar Lα phase by POPE-d31 (20 %) and PDPE-d31 (18 %) is resolved following the addition of α-toc. Order parameters in the remaining Lα phase are increased slightly more for POPE-d31 (7%) than PDPE-d31 (4%). Preferential interaction with polyunsaturated phospholipid is not apparent in these results. The propensity for α-toc to form phase structure with negative curvature that is more tightly packed at the membrane surface, nevertheless, may restrict the contact of free radicals with lipid chains on phosphatidylethanolamine molecules that accumulate polyunsaturated fatty acids.
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    α-Tocopherol is well designed to protect polyunsaturated fatty acids
    (Office of the Vice Chancellor for Research, 2014-04-11) Leng, Xiaoling; Williams, Justin A.; Marquardt, Drew; Kučerka, Norbert; Katsaras, John; Atkinson, Jeffrey; Harroun, Thad A.; Feller, Scott E.; Wassall, Stephen R.
    Polyunsaturated fatty acids (PUFA) are an influential constituent in cell membranes, but are extremely vulnerable to oxidation. The presumptive role for α-tocopherol (α-toc), the molecular form of vitamin E retained by the human body, is to protect PUFA-containing lipids from oxidation. To investigate whether α-toc preferentially interacts with PUFA in support of this function, we performed MD simulations on lipid bilayers composed of 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22-6PC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) in the presence of α-toc. SDPC with docosahexaenoic acid (DHA) for the sn-2 chain is polyunsaturated, while SOPC with oleic acid (OA) for the sn-2 chain serves as a monounsaturated control. The simulations were run at 37 °C under constant pressure for 200 ns on a system that comprised 80 phospholipid molecules, 20 α-toc molecules and 2165 water molecules. In qualitative agreement with our results from solid state 2H NMR and neutron scattering experiments, the simulations show that α-toc increases order inside the bilayer and that the chromanol headgroup sits near the surface in both SDPC and SOPC. Analyses of the density distribution of the lipid chains relative to α-toc show that the α-toc’s chromanol headgroup, the part of the molecule that protects against oxidation, would have more chance to interact with PUFA chains than saturated chains. A major prediction from our simulations is that α-toc undergoes flip-flop across the bilayer and that the rate is an order of magnitude greater in SDPC than SOPC. This is a remarkable finding that reveals a possible mechanism by which the chromanol group would not only wait at the membrane surface but would also patrol the membrane interior to meet lipid radicals and terminate the chain reaction by which lipid peroxidation proceeds.
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    β-Glucosylceramides and Tocopherols Regulate Development and Function of Dendritic Cells
    (American Association of Immunologists, 2022) Lajiness, Jacquelyn D.; Amarsaikhan, Nansalmaa; Tat, Kiet; Tsoggerel, Angar; Cook-Mills, Joan M.; Pediatrics, School of Medicine
    In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers) that are transported to the fetus via the placenta and to offspring via milk. The elevated βGlcCers increase numbers of fetal liver CD11c+CD11b+ dendritic cells (DCs) and offspring allergen-induced lung eosinophilia. These effects are modifiable by maternal dietary supplementation with the plant-derived lipids α-tocopherol and γ-tocopherol. It is not known whether βGlcCers and tocopherols directly regulate development of DCs. In this study, we demonstrated that βGlcCers increased development of GM-CSF-stimulated mouse bone marrow-derived DCs (BMDCs) in vitro without altering expression of costimulatory molecules. This increase in BMDC numbers was blocked by α-tocopherol and potentiated by γ-tocopherol. Furthermore, βGlcCers increased PKCα and PKCδ activation in BMDCs that was blocked by α-tocopherol. In contrast, γ-tocopherol increased BMDC PKCα and PKCδ activation and enhanced the βGlcCer-induced increase in PKCδ activation in a DC subset. Antigen processing per DC was minimally enhanced in βGlcCer-treated BMDCs and not altered ex vivo in lung DCs from pups of allergic mothers. Pups of allergic mothers had an increased proportion of CD11b+CD11c+ subsets of DCs, contributing to enhanced stimulation of T cell proliferation ex vivo. Thus, βGlcCer, which is both necessary and sufficient for development of allergic predisposition in offspring of allergic mothers, directly increased development and PKC activation in BMDCs. Furthermore, this was modifiable by dietary tocopherols. This may inform design of future studies for the prevention or intervention in asthma and allergic disease.