Modulation of Proteasome Activity by Vitamin E in THP‐1 Monocytes

Munteanu, Adelina; Ricciarelli, Roberta; Massone, Sara; Zingg, Jean-Marc

doi:10.1080/15216540701697420

Cited by 14 publications

(9 citation statements)

References 53 publications

(95 reference statements)

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“…Since both αTP and γTP are formed in the in vitro assay, it was interesting to determine whether the two compounds affect cells with different potency, what could contribute to the activity differences seen with αT and γT in THP-1 monocytic leukaemia cells [4], [36] and other experimental systems despite a generally lower γT level (reviewed in [37]). When THP-1 cells were incubated with either αTP or γTP at increasing concentrations for 4, 28 or 52 h, γTP inhibited their proliferation more efficiently than αTP (Figure 2A); concentrations of γTP above 20 µM led to cell loss due to cytotoxic/apoptotic effects, what occurred with αTP only at concentrations above 46 µM [31].…”

Section: Resultsmentioning

confidence: 99%

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

et al. 2014

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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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Section: Resultsmentioning

confidence: 99%

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

et al. 2014

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“…aTP inhibits cellular proteasome activity in THP-1 monocytes [93], and stimulates telomerase activity with consequent prevention of telomere shortening [30]; however, the in vivo relevance and the molecular mechanisms involved are not known but could contribute to the anti-aging effects seen with vitamin E [94,95]. Contrary to aT, aTP is cytotoxic to THP-1 monocytes and murine MG-63 melanoma cells [92,96], but cytotoxicity and apoptosis is only observed at high concentrations (450 mM), possibly reflecting an activity seen with synthetic vitamin E derivatives, such as aTS or 2,5,7,8-tetramethyl-2R-(4R,8R,1 2-trimethyltridecyl) chroman-6-yloxy acetic acid (reviewed in [11]).…”

Section: Biological Activities Of Atpmentioning

confidence: 99%

α‐Tocopheryl phosphate – An active lipid mediator?

Zingg

Meydani

Azzi

2010

Molecular Nutrition Food Res

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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.

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“…97), alternative usage of initiation sites for VEGF transcription and translation [98], alternative splicing of VEGF [99], stabilization of the VEGF mRNA by RNA binding proteins [100][101][102], possible interference of aTP with the activity of inhibitory miRNA targeting VEGF mRNA [103,104], activation of the unfolded protein response important for angiogenesis in the developing placenta [105], or inhibition of proteasome by aTP leading to increased levels of VEGF or HIF-1a [106].…”

Section: Possible Molecular Mechanisms Of Vegf Induction By Atpmentioning

confidence: 99%

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

2012

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Vitamin E was originally discovered as a dietary factor essential for reproduction in rats. Since then, vitamin E has revealed many important molecular properties such as the scavenging of reactive oxygen and nitrogen species or the modulation of signal transduction and gene expression in antioxidant and nonantioxidant manners. A congenital disease, ataxia with vitamin E deficiency, which is characterized by impaired enrichment of α-tocopherol (αT) in plasma due to mutations in the α-tocopherol transfer protein gene, has been discovered. An effect of vitamin E on angiogenesis and vasculogenesis has been observed in several studies, and recently, it has been demonstrated in the placenta of pregnant ewes, possibly involving the stimulation of vascular endothelial growth factor (VEGF) expression. We recently observed that the phosphorylated form of αT, α-tocopheryl phosphate (αTP), increases the expression of VEGF. We propose that the stimulatory effect of αT on angiogenesis and vasculogenesis is potentiated by phosphorylation to αTP, which may act as a cofactor or active lipid mediator increasing VEGF expression. Increased VEGF expression and consequent enhanced angiogenesis and vasculogenesis induced by αTP may explain not only the essential roles of vitamin E on reproduction, but also its beneficial effects against pre-eclampsia, ischemia/reperfusion injury, and during wound healing. It may also serve as a survival factor for brain and muscle cells. The finding that αTP may regulate vasculogenesis may indicate potential, important pathophysiological implications.

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Modulation of Proteasome Activity by Vitamin E in THP‐1 Monocytes

Cited by 14 publications

References 53 publications

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

α‐Tocopheryl phosphate – An active lipid mediator?

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

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