The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
Angelo Azzi - One of the best experts on this subject based on the ideXlab platform.
-
The role of Alpha-Tocopherol in preventing disease.
European journal of nutrition, 2020Co-Authors: Angelo AzziAbstract:A role of oxidative stress in atherosclerosis lies on experimental results carried out in vitro and in animal models. In humans, the supplementation with the antioxidant vitamin E has given in some cases supportive results and in others no effects. From in vitro studies, a large amount of data has shown that Alpha-Tocopherol (the major component of vitamin E) regulates key events in the cellular pathogenesis of atherosclerosis. We first described the inhibition of protein kinase C (PKC) activity by Alpha-Tocopherol to be at the basis of the vascular smooth muscle cell growth inhibition by this compound. Subsequently, PKC was recognized to be the target of Alpha-Tocopherol in different cell types, including monocytes, macrophages, neutrophils, fibroblasts and mesangial cells. Inhibiting the activity of protein kinase C by Alpha-Tocopherol results in different events in different cell types: inhibition of platelet aggregation, of nitric oxide production in endothelial cells, of superoxide production in neutrophils and macrophages as well as impairment of smooth muscle cell proliferation. Adhesion molecule expression and inflammatory cell cytokine production are also influenced by Alpha-Tocopherol. Scavenger receptors, particularly important in the formation of atherosclerotic foam cells, are also modulated by Alpha-Tocopherol. The oxidized LDL scavenger receptors SR-A and CD36 are down regulated at the transcriptional level by Alpha-Tocopherol. The relevance of CD36 expression in the onset of atherosclerosis has been indicated by the protection against atherosclerosis by CD36 knockout mice. In conclusion, the effect of Alpha-Tocopherol against atherosclerosis is not due only to the prevention of LDL oxidation but also to the down regulation of the scavenger receptor CD36 and to the inhibition of PKC activity.
-
Regulation of gene expression by Alpha-Tocopherol
Biol Chem, 2004Co-Authors: Angelo Azzi, P Kempna, L Villacorta, T Visarius, René Gysin, Adrian Munteanu, J M ZinggAbstract:Several genes are regulated by tocopherols which can be categorized, based on their function, into five groups: genes that are involved in the uptake and degradation of tocopherols (Group 1) include Alpha-Tocopherol transfer protein (alpha-TTP) and cytochrome P450 (CYP3A); genes that are associated with lipid uptake and atherosclerosis (Group 2) include CD36, SR-BI and SR-AI/II. Genes that modulate the expression of extracellular proteins (Group 3) include tropomyosin, collagen(alpha1), MMP-1, MMP-19 and connective tissue growth factor (CTGF). Genes that are related to inflammation, cell adhesion and platelet aggregation (Group 4) include E-selectin, ICAM-1, integrins, glycoprotein IIb, II-2, IL-4 and IL-beta. Group 5 comprises genes coding for proteins involved in cell signaling and cell cycle regulation and consists of PPAR-gamma, cyclin D1, cyclin E, Bcl2-L1, p27 and CD95 (Apo-1/Fas ligand). The expression of P27, Bcl2, alpha-TTP, CYP3A, tropomyosin, II-2, PPAR-gamma, and CTGF appears to be up-regulated by one or more tocopherols whereas all other listed genes are down-regulated. Several mechanisms may underlie tocopherol-dependent gene regulation. In some cases protein kinase C has been implicated due to its deactivation by Alpha-Tocopherol and its participation in the regulation of a number of transcription factors (NF-kappaB, AP-1). In other cases a direct involvement of PXR/RXR has been documented. The antioxidant responsive element (ARE) appears in some cases to be involved as well as the transforming growth factor beta responsive element (TGF-beta-RE). This heterogeneity of mediators of tocopherol action suggests the need of a common element that could be a receptor or a co-receptor, able to interact with tocopherol and with transcription factors directed toward specific regions of promoter sequences of sensitive genes. Here we review recent results of the search for molecular mechanisms underpinning the central signaling mechanism.
-
Non-antioxidant molecular functions of Alpha-Tocopherol (vitamin E).
FEBS letters, 2002Co-Authors: Angelo Azzi, Roberta Ricciarelli, J M ZinggAbstract:Alpha-Tocopherol (the major vitamin E component) regulates key cellular events by mechanisms unrelated with its antioxidant function. Inhibition of protein kinase C (PKC) activity and vascular smooth muscle cell growth by Alpha-Tocopherol was first described by our group. Later, Alpha-Tocopherol was shown to inhibit PKC in various cell types with consequent inhibition of aggregation in platelets, of nitric oxide production in endothelial cells and of superoxide production in neutrophils and macrophages. Alpha-Tocopherol diminishes adhesion molecule, collagenase and scavenger receptor (SR-A and CD36) expression and increases connective tissue growth factor expression.
-
Signalling functions of Alpha-Tocopherol in smooth muscle cells.
International Journal for Vitamin and Nutrition Research, 1997Co-Authors: Angelo Azzi, A Tasinato, Daniel Boscoboinik, Sophie Clément, Nesrin Kartal Ozer, Roberta Ricciarelli, Achim Stocker, Onder SirikciAbstract:Alpha-Tocopherol but not beta-tocopherol, activates protein phosphatase 2A, decreases protein kinase C activity and attenuates smooth muscle cell proliferation at physiological concentrations. beta-Tocopherol prevents the effects of Alpha-Tocopherol. Inhibition of protein kinase C alpha, but not of the other isoforms, by the inhibitor Go6976 prevents the effect of Alpha-Tocopherol. Protein kinase C alpha, immunoprecipitated from Alpha-Tocopherol treated cells, is less phosphorylated and inactive. It is proposed that the specific activation of protein phosphatase 2A by Alpha-Tocopherol results in dephosphorylation and inactivation of protein kinase C alpha. Finally, this cascade of events leads to smooth muscle cell proliferation inhibition.
-
Inhibition of cell proliferation by Alpha-Tocopherol. Role of protein kinase C.
Journal of Biological Chemistry, 1991Co-Authors: Daniel Boscoboinik, Adam Szewczyk, Carmel Hensey, Angelo AzziAbstract:Abstract The effect of Alpha-Tocopherol (vitamin E) on the proliferation of vascular smooth muscle cells (A7r5), human osteosarcoma cells (Saos-2), fibroblasts (Balb/3T3), and neuroblastoma cells (NB2A) has been studied. The proliferation of vascular smooth muscle cells was inhibited by physiologically relevant concentrations of Alpha-Tocopherol, neuroblastoma cells were only sensitive to higher Alpha-Tocopherol concentrations, and proliferation of the other cell lines was not inhibited. The inhibition of smooth muscle cell proliferation was specific for Alpha-Tocopherol. Trolox, phytol, and Alpha-Tocopherol esters had no effect. Proliferation of smooth muscle cells stimulated by platelet-derived growth factor or endothelin was completely sensitive to Alpha-Tocopherol. If smooth muscle cells were stimulated by fetal calf serum, proliferation was 50% inhibited by Alpha-Tocopherol. No effect of Alpha-Tocopherol was observed when proliferation of smooth muscle cells was stimulated by bombesin and lysophosphatidic acid. The possibility of an involvement of protein kinase C in the cell response to Alpha-Tocopherol was suggested by experiments with the isolated enzyme and supported by the 2- to 3-fold stimulation of phorbol ester binding induced by Alpha-Tocopherol in sensitive cells. Moreover, Alpha-Tocopherol also caused inhibition of protein kinase C translocation induced by phorbol esters and inhibition of the phosphorylation of its 80-kDa protein substrate in smooth muscle cells. A model is discussed by which Alpha-Tocopherol inhibits cell proliferation by interacting with the cytosolic protein kinase C, thus preventing its membrane translocation and activation.
J M Zingg - One of the best experts on this subject based on the ideXlab platform.
-
Regulation of gene expression by Alpha-Tocopherol
Biol Chem, 2004Co-Authors: Angelo Azzi, P Kempna, L Villacorta, T Visarius, René Gysin, Adrian Munteanu, J M ZinggAbstract:Several genes are regulated by tocopherols which can be categorized, based on their function, into five groups: genes that are involved in the uptake and degradation of tocopherols (Group 1) include Alpha-Tocopherol transfer protein (alpha-TTP) and cytochrome P450 (CYP3A); genes that are associated with lipid uptake and atherosclerosis (Group 2) include CD36, SR-BI and SR-AI/II. Genes that modulate the expression of extracellular proteins (Group 3) include tropomyosin, collagen(alpha1), MMP-1, MMP-19 and connective tissue growth factor (CTGF). Genes that are related to inflammation, cell adhesion and platelet aggregation (Group 4) include E-selectin, ICAM-1, integrins, glycoprotein IIb, II-2, IL-4 and IL-beta. Group 5 comprises genes coding for proteins involved in cell signaling and cell cycle regulation and consists of PPAR-gamma, cyclin D1, cyclin E, Bcl2-L1, p27 and CD95 (Apo-1/Fas ligand). The expression of P27, Bcl2, alpha-TTP, CYP3A, tropomyosin, II-2, PPAR-gamma, and CTGF appears to be up-regulated by one or more tocopherols whereas all other listed genes are down-regulated. Several mechanisms may underlie tocopherol-dependent gene regulation. In some cases protein kinase C has been implicated due to its deactivation by Alpha-Tocopherol and its participation in the regulation of a number of transcription factors (NF-kappaB, AP-1). In other cases a direct involvement of PXR/RXR has been documented. The antioxidant responsive element (ARE) appears in some cases to be involved as well as the transforming growth factor beta responsive element (TGF-beta-RE). This heterogeneity of mediators of tocopherol action suggests the need of a common element that could be a receptor or a co-receptor, able to interact with tocopherol and with transcription factors directed toward specific regions of promoter sequences of sensitive genes. Here we review recent results of the search for molecular mechanisms underpinning the central signaling mechanism.
-
Non-antioxidant molecular functions of Alpha-Tocopherol (vitamin E).
FEBS letters, 2002Co-Authors: Angelo Azzi, Roberta Ricciarelli, J M ZinggAbstract:Alpha-Tocopherol (the major vitamin E component) regulates key cellular events by mechanisms unrelated with its antioxidant function. Inhibition of protein kinase C (PKC) activity and vascular smooth muscle cell growth by Alpha-Tocopherol was first described by our group. Later, Alpha-Tocopherol was shown to inhibit PKC in various cell types with consequent inhibition of aggregation in platelets, of nitric oxide production in endothelial cells and of superoxide production in neutrophils and macrophages. Alpha-Tocopherol diminishes adhesion molecule, collagenase and scavenger receptor (SR-A and CD36) expression and increases connective tissue growth factor expression.
A Tasinato - One of the best experts on this subject based on the ideXlab platform.
-
RRR-Alpha-Tocopherol regulation of gene transcription in response to the cell oxidant status.
Zeitschrift fur Ernahrungswissenschaft, 1998Co-Authors: A Azzi, D Boscoboinik, A Fazzio, D Marilley, P Maroni, N K Ozer, S Spycher, A TasinatoAbstract:RRR-Alpha-Tocopherol, but not RRR-beta-tocopherol, negative regulates proliferation of vascular smooth muscle cells at physiological concentrations. At the same concentrations RRR-Alpha-Tocopherol inhibits protein kinase C activity, whereas RRR-beta-tocopherol is ineffective. Furthermore, RRR-beta-tocopherol prevents the inhibition of cell growth and of protein kinase C activity caused by RRR-Alpha-Tocopherol. The negative regulation by RRR-Alpha-Tocopherol of protein kinase C activity appears to be the cause of smooth muscle cell growth inhibition. RRR-Alpha-Tocopherol does not act by binding to protein kinase C directly but presumably by preventing protein kinase C activation. A second RRR-Alpha-Tocopherol effect has been found at the level of AP 1, the latter becoming activated by RRR-Alpha-Tocopherol under condition of protein kinase C inhibition or down regulation. AP-1 inhibition by RRR-Alpha-Tocopherol is seen, however, under condition of protein kinase C stimulation. Compositional changes of AP-1 have been found to be at the basis of the RRR-Alpha-Tocopherol effects. RRR-beta-tocopherol, provided with similar antioxidant properties, not only it does not affect AP 1 but it prevents the effects of RRR-Alpha-Tocopherol. Moreover, it has been observed that RRR-Alpha-Tocopherol is able to affect TRE regulated gene transcription. It is concluded that RRR-Alpha-Tocopherol acts specifically in vascular smooth muscle cells, by controlling a signal transduction pathway leading to cell proliferation by a non-antioxidant mechanism.
-
Signalling functions of Alpha-Tocopherol in smooth muscle cells.
International Journal for Vitamin and Nutrition Research, 1997Co-Authors: Angelo Azzi, A Tasinato, Daniel Boscoboinik, Sophie Clément, Nesrin Kartal Ozer, Roberta Ricciarelli, Achim Stocker, Onder SirikciAbstract:Alpha-Tocopherol but not beta-tocopherol, activates protein phosphatase 2A, decreases protein kinase C activity and attenuates smooth muscle cell proliferation at physiological concentrations. beta-Tocopherol prevents the effects of Alpha-Tocopherol. Inhibition of protein kinase C alpha, but not of the other isoforms, by the inhibitor Go6976 prevents the effect of Alpha-Tocopherol. Protein kinase C alpha, immunoprecipitated from Alpha-Tocopherol treated cells, is less phosphorylated and inactive. It is proposed that the specific activation of protein phosphatase 2A by Alpha-Tocopherol results in dephosphorylation and inactivation of protein kinase C alpha. Finally, this cascade of events leads to smooth muscle cell proliferation inhibition.
-
Alpha-Tocopherol as a modulator of smooth muscle cell proliferation.
Prostaglandins leukotrienes and essential fatty acids, 1997Co-Authors: A Azzi, D Boscoboinik, D Marilley, N K Ozer, Sophie Clément, Roberta Ricciarelli, A TasinatoAbstract:The effects of Alpha-Tocopherol and beta-tocopherol have been studied in rat and human aortic smooth muscle cells. Alpha-Tocopherol, but not beta-tocopherol, inhibited smooth muscle cell proliferation and protein kinase C in a dose-dependent manner, at concentrations ranging from 10 to 50 microM. Beta-tocopherol added simultaneously with Alpha-Tocopherol prevented both proliferation and protein kinase C inhibition. Protein kinase C inhibition was cell cycle-dependent and it was prevented by okadaic acid, a protein phosphatase inhibitor. Protein kinase C activity measured from aortas of cholesterol-fed rabbits was also inhibited by Alpha-Tocopherol. By using protein kinase C (PKC) isoform-specific inhibitors and immunoprecipitation reactions it was found that PKC-alpha was selectively inhibited by Alpha-Tocopherol. Further, an activation of protein phosphatase 2A by Alpha-Tocopherol was found, which caused PKC-alpha dephosphorylation and inhibition. Ultimately, this cascade of events at the level of cell signal transduction leads to the inhibition of smooth muscle cell proliferation.
Ephrem Eggermont - One of the best experts on this subject based on the ideXlab platform.
-
Recent advances in vitamin E metabolism and deficiency
European Journal of Pediatrics, 2006Co-Authors: Ephrem EggermontAbstract:Alpha-, beta-, gamma- and delta-tocopherol are present in many foods and are, in the absence of fat malabsorption, well absorbed from the gut. Their anti-oxidant property is well known and protects arteries and capillaries as well as blood lipids and nervous tissue against oxidative stress. In contrast to beta-, gamma- and delta-tocopherol, Alpha-Tocopherol is preferentially conserved by the discriminating action of the liver Alpha-Tocopherol transfer protein, which also maintains plasma Alpha-Tocopherol concentration within a range of 20 to 40 μ M . In the circulation, Alpha-Tocopherol, in association with the transfer-protein, is assembled into the very low-density lipoprotein and low-density liprotein particles and released for use by the peripheral tissues. Recent data suggest that Alpha-Tocopherol is not only an anti-oxidant but also a regulator of gene expression through its binding to nuclear receptors. The precise mechanism of regulating gene expression, however, is still unknown. The four tocopherols are ultimately degraded by omega-oxidation and subsequent beta-oxidations followed by the elimination of the metabolites in the bile and in the urine. Patients with a defect of the Alpha-Tocopherol transfer protein are unable to maintain their Alpha-Tocopherol reserves and progressively lose tendon reflexes and have signs and symptoms of spinocerebellar ataxia while plasma vitamin E level drops below 2 μg/ml.
Kenneth Blum - One of the best experts on this subject based on the ideXlab platform.
-
Changes in plasma carotenoid, Alpha-Tocopherol, and lipid peroxide levels in response to supplementation with concentrated fruit and vegetable extracts: a pilot study
Topics in Catalysis, 1996Co-Authors: John A. Wise, Robert J. Morin, Roger Sanderson, Kenneth BlumAbstract:Studies over the last two decades equating diet with chronic diseases have linked the highest consumption of mixed fruits and vegetables to a reduced risk of coronary heart disease (CHD), stroke, cataracts, and cancer at multiple sites. High levels of natural antioxidants, including the carotenoids, tocopherols, and ascorbic acid, appear to be responsible for these reductions in risk. However, long-term intervention studies to alter chronic disease outcomes have generally used a single nutrient such as beta-carotene at high doses, and results have been disappointing. Because antioxidants have multiple and synergistic interactions and also exhibit compartmentalization and tissue specificity, it appears desirable to use supplementation that increases blood levels while stimulating combinations of these chemoprotective substances in amounts more closely approximating amounts of mixed diets. This study measured carotenoid and tocopherol levels in human plasma after supplementation with dehydrated fruit and vegetable extracts (JuicePlus+ ™). Serum lipid peroxides were also measured to assess the effectiveness of supplementation in modifying oxidative processes. Fifteen healthy adults (10 women, 5 men; age range, 18 to 53 years) consumed supplements twice daily with meals for 28 days, with fasting plasma and serum samples taken at baseline and 7, 14, and 28 days. After 28 days, plasma antioxidant levels increased significantly: beta-carotene, 510%; alpha-carotene, 119%; lutein/zeaxanthin, 44%; lycopene, 2046%; and Alpha-Tocopherol, 58%. Serum lipid peroxides decreased fourfold after 7 days and remained significantly lower than baseline at 28 days (baseline, 16.85 ± 16.91 μmol/mL; 28 days, 4.22 ± 3.78 μmol/mL). Decreases in lipid peroxide levels were coincident with increases in carotenoids and Alpha-Tocopherol, and reflect functionally improved oxidative defense mechanisms. Because these bioactive compounds can act synergistically, the effect cannot be attributed to any one component, but it may reflect a combined mechanism of antioxidant defense. Marked increases in plasma levels of predominant dietary carotenoids and Alpha-Tocopherol in all subjects indicate that supplementation with fruit and vegetable concentrates may prove effective in future intervention studies. © 1996, All rights reserved.