Modulation of gene expression by α-tocopherol and α-tocopheryl phosphate in THP-1 monocytes

Zingg, Jean Marc; Libinaki, Roksan; Lai, Chao‐Qiang; Meydani, Mohsen; Gianello, Robert; Ogru, Esra; Azzi, Angelo

doi:10.1016/j.freeradbiomed.2010.09.034

Cited by 49 publications

(93 citation statements)

References 79 publications

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“…In our model system, aTP increased angiogenesis in endothelial cells by increasing VEGF production by monocytes, and no direct proangiogenic or antiangiogenic effect on endothelial cells was observed during the time of the angiogenesis assay [70]. Induction of VEGF by aTP was the consequence of stimulation of the PI3K/Akt signaling pathway, a pathway that is prone to down-regulation by aT [71].…”

Section: Introductionmentioning

confidence: 74%

“…Using THP-1 monocytes, we recently observed that the phosphorylated form of aT and aTP induced VEGF expression at the mRNA and protein level leading to increased in vitro angiogenesis in HUVEC, whereas aT was not effective [70] presumably as a consequence of a low ''aT kinase'' activity in these cells. In our model system, aTP increased angiogenesis in endothelial cells by increasing VEGF production by monocytes, and no direct proangiogenic or antiangiogenic effect on endothelial cells was observed during the time of the angiogenesis assay [70].…”

Section: Introductionmentioning

confidence: 99%

“…Relative to aT, aTP's presence in food occurs in low amounts [80], its uptake as an intact molecule is much less efficient than that of aT even when given as supplement, and its tissue levels are low as most of it is hydrolyzed to aT, suggesting that it is not a transport or storage form of aT [70,[81][82][83][84]. A local synthesis of aTP in specific cells may thus be necessary to allow the position of aTP at specific subcellular sites relevant for signaling.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2012

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“…As vitamin E is a potent antioxidant with anti-inflammatory properties, several lines www.intechopen.com of evidence suggest that -tocopherol has also potential beneficial effects with regard to cardiovascular disease (Singh et al, 2005;Rodrigo et al, 2008). A recent study has also demonstrated that natural vitamin E analog alpha-tocopheryl phosphate (alphaTP) modulates atherosclerotic and inflammatory events through the regulation of certain genes (Zingg et al, 2010). However, it is also important to point out that the non-antioxidant activities of tocopherols may also represent the main biological reason for the selective retention of alpha-tocopherol in the body, or vice versa, for the metabolic conversion and consequent elimination of the other tocopherols (Zingg et al, 2004).…”

Section: Vitamins With Antioxidant Properties: Vitamin E and Vitamin Cmentioning

confidence: 99%

Compounds with Antioxidant Capacity as Potential Tools Against Several Oxidative Stress Related Disorders: Fact or Artifact?

Pérez-Matute¹,

Crujeiras²,

Fernández‐Galilea³

et al. 2012

Oxidative Stress and Diseases

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Oxidative Stress and Diseases 544 reactive species: reactive oxygen species (ROS, thus, oxygen-containing molecules that are highly reactive), reactive chlorine species (RCN) and reactive nitrogen species (RNS). All these reactants contain free radicals as well as nonradicals. Low concentrations of these reactive species are necessary for normal cell redox status, cell function and intracellular signalling (Droge, 2002;Valko et al., 2007;Perez-Matute et al., 2009). However, in some disease states, free radicals are produced in excess and can damage DNA, proteins, carbohydrates and lipid constituents and compromise cell function leading to the development of type 2 diabetes, atherosclerosis, obesity, arthritis etc. Thus, it is clear that excessive production of free radicals causes damage to biological material and is an essential event in the aetiopathogenesis of various diseases. However, the question that has risen in the past years is whether uncontrolled formation of ROS is a primary cause or a downstream consequence of the pathological processes. In other words, it is still not clear what comes first, the chicken or the egg. However, what is clear is that there must be a balance between these reactive species and the antioxidants, whose main function is to counteract the deleterious effects of these reactive species. In fact, antioxidant is defined as any substance that when present at low concentrations compared with those of an oxidizable substrate, significantly delays or prevents oxidation of that substrate (Halliwell & Gutteridge, 1999). These defences include both enzymatic (superoxide dismutases, glutathione peroxidase, catalase, thioredoxin) and non-enzimatic systems (vitamins such as vitamin C, E, A, minerals such as selenium, zinc, cooper, bilirrubine, uric acid, some aminoacids etc).Several studies have demonstrated an increased oxidative state (either caused by an increased ROS production or diminished levels of antioxidants) in serious pathologies such as obesity, cardiovascular diseases, metabolic syndrome, cancer etc. Thus, oxidative stress actually may be related with the mentioned processes. In this context, it is tempting to suggest that if oxidative damage significantly contributes to disease pathology, then, actions that decrease it (via decreasing ROS production or increasing endogenous levels of antioxidants) might be therapeutically beneficial. In fact, attenuation or complete suppression of oxidative stress as a way to improve several diseases has flourished as one of the main challenges of research in the last years. Thus, several approaches have been carried out in order to either decrease the high levels of ROS generated or boost the endogenous levels of antioxiants. Inhibition of ROS production through the development of inhibitors (natural or chemical) against the main sources of ROS generation offers an interesting approach. Thus, NADPH oxidase and mitochondria have been postulated as the main targets to reduce ROS production (reviewed by Pérez-Matute et al., 2009). Another str...

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“…In addition, aT and more so phosphorylated aT (aTP) stimulate PI3Kgamma (PI3Kg) activity by facilitating hTAP1-mediated PI exchange and presentation to the enzyme and/or by dissociation of an inactive heterodimer (5). Activation of the PI3Kg/protein kinase B (PKB) signal transduction pathway by aTP induces the expression of a number of genes such as the vascular endothelial growth factor (VEGF) which is important for angiogenesis, vasculogenesis and cell survival (6,7). Thus, vitamin E may act as active lipid mediator by liberating PI from hTAPs and making it accessible to phosphorylation by PI3Kg, a function that may be necessary for its essentiality as a vitamin.…”

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confidence: 99%

Modulation of Signal Transduction and Gene Expression by Vitamin E via PI3Kγ/PKB and hTAP1/SEC14L2-Mediated Lipid Exchange

Zingg

2015

J Nutr Sci Vitaminol

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SummaryThe ability of vitamin E to modulate signal transduction and gene expression has been observed in numerous cell culture and animal studies. These cellular signalling effects of vitamin E have been mainly explained as result of protection of lipids and signal transduction enzymes from random modification by free radicals or by specifically influencing their redox state. Alternatively, the observed signalling may reflect specific interactions of vitamin E with enzymes, structural proteins, and transcription factors and/or result from vitamin E-induced alterations of physical and structural properties of membrane lipid domains in which it is embedded. A novel signal transduction mechanism of vitamin E is proposed in which lipid transfer proteins (LTP) facilitate phosphorylation of phosphatidylinositol by exchanging it with vitamin E and presenting it to phosphatidylinositol-3-kinase (PI3K).

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Modulation of gene expression by α-tocopherol and α-tocopheryl phosphate in THP-1 monocytes

Cited by 49 publications

References 79 publications

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

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

Compounds with Antioxidant Capacity as Potential Tools Against Several Oxidative Stress Related Disorders: Fact or Artifact?

Modulation of Signal Transduction and Gene Expression by Vitamin E via PI3Kγ/PKB and hTAP1/SEC14L2-Mediated Lipid Exchange

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Modulation of gene expression by α-tocopherol and α-tocopheryl phosphate in THP-1 monocytes

Cited by 49 publications

References 79 publications

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

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

Compounds with Antioxidant Capacity as Potential Tools Against Several Oxidative Stress Related Disorders: Fact or Artifact?

Modulation of Signal Transduction and Gene Expression by Vitamin E via PI3K&gamma;/PKB and hTAP1/SEC14L2-Mediated Lipid Exchange

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Modulation of Signal Transduction and Gene Expression by Vitamin E via PI3Kγ/PKB and hTAP1/SEC14L2-Mediated Lipid Exchange