35 research outputs found
Changes in Bioavailability of Omega-3 (DHA) through Alpha-Tocopheryl Phosphate Mixture (TPM) after Oral Administration in Rats
Benefits of Omega-3 Docosahexaenoic acid (DHA) supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM), following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg) or low dose (88.6 mg/kg) of DHA. TPM was examined at 1:0.1 w/w (low TPM dose) and 1:0.5 w/w (high TPM dose). Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL) and AUC values (1396.60 and 1560.60) for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont) and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns) and 50% (p < 0.05) increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90%) the LDC control (p = 0.057). This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products
Modulation of phosphorylation of tocopherol and phosphatidylinositol by hTAP1/SEC14L2-mediated lipid exchange
The vitamin E derivative, alpha-tocopheryl phosphate (αTP), is detectable in cultured cells, plasma and tissues in small amounts, suggesting the existence of enzyme(s) with α-tocopherol (αT) kinase activity. Here, we characterize the production of αTP from αT and [γ-32P]-ATP in primary human coronary artery smooth muscle cells (HCA-SMC) using separation by thin layer chromatography (TLC) and subsequent analysis by Ultra Performance Liquid Chromatography (UPLC). In addition to αT, although to a lower amount, also γT is phosphorylated. In THP-1 monocytes, γTP inhibits cell proliferation and reduces CD36 scavenger receptor expression more potently than αTP. Both αTP and γTP activate the promoter of the human vascular endothelial growth factor (VEGF) gene with similar potency, whereas αT and γT had no significant effect. The recombinant human tocopherol associated protein 1 (hTAP1, hSEC14L2) binds both αT and αTP and stimulates phosphorylation of αT possibly by facilitating its transport and presentation to a putative αT kinase. Recombinant hTAP1 reduces the in vitro activity of the phosphatidylinositol-3-kinase gamma (PI3Kγ) indicating the formation of a stalled/inactive hTAP1/PI3Kγ heterodimer. The addition of αT, βT, γT, δT or αTP differentially stimulates PI3Kγ, suggesting facilitated egress of sequestered PI from hTAP1 to the enzyme. It is suggested that the continuous competitive exchange of different lipophilic ligands in hTAPs with cell enzymes and membranes may be a way to make these lipophiles more accessible as substrates for enzymes and as components of specific membrane domains
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Vitamin E and Cancer
Protection by vitamin E against free radical-induced DNA mutations appears not to be an effective occurrence. On the other hand, in vitro evidence that different tocopherols slow down cell proliferation is an accepted observation. However, such an event may not be sufficient to result in beneficial clinical outcomes. Tocopheryl phosphate, a more active, natural derivative of tocopherol, endowed with prevention and therapeutic potential, represents a possible key to the understanding of the present conflict between laboratory and clinical results
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On the existence of cellular tocopheryl phosphate, its synthesis, degradation and cellular roles: A hypothesis
The finding that alpha-tocopheryl phosphate is present in cells in small amounts, that it can be synthesized and hydrolyzed supports the hypothesis that alpha-tocopheryl phosphate might be a signaling molecule. The possible pathways needed for the synthesis, hydrolysis and signaling are considered in this hypothesis as well the possible extension of this reaction to additional molecules such as tocopherols and tocotrienols. A possible mechanism of action of other tocopherol esters (succinate and maleate) is also hypothesized
Primary human coronary artery smooth muscle cells (HCA-SMC) contain αT phosphorylation activity.
<p>(A) HCA-SMC cells were treated with 0.1% ethanol control (c) or αT, and the <i>in situ</i> phosphorylation reaction, lipid extraction, and thin layer chromatography performed as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101550#s2" target="_blank">materials and methods</a>. The TLC plate was subsequently exposed to film, and the labeled sample spots and control spots separated in parallel were scraped, extracted and the presence of αTP confirmed by UPLC (lower part). (B) Specificity of the αT phosphorylation reaction, concentration dependency and substrate specificity of αT phosphorylation. HCA-SMC cells were treated with 0.1% ethanol control (c) or αT, αTP, αTQ at the indicated concentrations, and the phosphorylation reaction, lipid extraction, and thin layer chromatography (TLC) were performed as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101550#s2" target="_blank">materials and methods</a>. (C) Comparison of αT and γT phosphorylation (mean±SEM, n = 2, *<i>P</i><0.05 relative to control (c)).</p