α‐Tocopheryl phosphate – An active lipid mediator?

Abstract

The vitamin E (alpha-tocopherol, alphaT) derivative, alpha-tocopheryl phosphate (alphaTP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that alphaT can become phosphorylated and alphaTP dephosphorylated, suggesting the existence of enzyme(s) with alphaT kinase or alphaTP phosphatase activity, respectively. As a supplement in animal studies, alphaTP can reach plasma concentrations similar to alphaT and only a part is dephosphorylated; thus, alphaTP may act both as pro-vitamin E, but also as phosphorylated form of vitamin E with possibly novel regulatory activities. Many effects of alphaTP have been described: in the test tube alphaTP modulates the activity of several enzymes; in cell culture alphaTP affects proliferation, apoptosis, signal transduction, and gene expression; in animal studies alphaTP prevents atherosclerosis, ischemia/reperfusion injury, and induces hippocampal long-term potentiation. At the molecular level, alphaTP may act as a cofactor for enzymes, as an active lipid mediator similar to other phosphorylated lipids, or indirectly by altering membrane characteristics such as lipid rafts, fluidity, and curvature. In this review, the molecular and cellular activities of alphaTP are examined and the possible functions of alphaTP as a natural compound, cofactor and active lipid mediator involved in signal transduction and gene expression discussed.

α‐Tocopheryl phosphate—An activated form of vitamin E important for angiogenesis and vasculogenesis?

“…110). The demonstration that aTP increases VEGF, angiogenesis, and vasculogenesis in the labyrinthine trophoblast could explain, at the molecular level, a phenomenon first observed almost 100 years ago by Evans and Bishop whose investigation of dietary factors essential for reproduction in rats led to the discovery of the essentiality of vitamin E [5].…”

“…However, uptake of intact aTP from the diet is not very efficient, and its possible hydrolysis in the gastrointestinal track and in tissues may not lead to unequivocal results [70,110,111]. This could be minimized by using the validated in vitro human placental veins angiogenesis model with disks isolated from human placentas or from vitamin E deficient wild-type or a-TTP (À/À) knockout mice [112].…”

“…We recently identified aTP as a natural derivative of aT with higher potency on signal transduction and the regulation of gene expression, such as the induction of VEGF expression (reviewed in ref. 110).…”

Vitamin E, signalosomes and gene expression in T cells

“…In this regard, it is known that a-tocopherol is able to modulate a number of cell functions in a unique way, not shared by other antioxidant nutrients (Azzi, 2007). Furthermore, some studies indicate that a-tocopherol is phosphorylated and that this phosphorylated derivative could be an active lipid mediator (Zingg et al, 2010). Employing a microarray analysis, Han et al (2006) compared the gene expression profiles of purified T cells from young and old mice fed a 30 ppm (control) or 500 ppm (supplemented) vitamin E-diet for 4 weeks.…”

Vitamin E: A Role in Signal Transduction

“…The biological function of αTP is not clear to date; it may act as a cofactor for enzymes, as a ligand of a receptor or a transcription factor, or as a "second www.annualreviews.org • Mechanisms of Signaling by Vitamin E CEHC: carboxyethyl hydroxychroman messenger" in the membrane, capable of exerting regulatory effects (reviewed in 165,280). Only small amounts of αTP are formed from αT by a putative αT kinase in cultured cells, plasma, and animal tissues, and an αTP phosphatase or esterase has been postulated for the dephosphorylation reaction (72,108,162,165,171).…”