Modulation of cell proliferation and gene expression by α-tocopheryl phosphates: relevance to atherosclerosis and inflammation

Munteanu, Adelina; Zingg, Jean‐Marc; Ogru, Esra; Libinaki, Roksan; Gianello, Robert; West, Simon; Negis, Yesim; Azzi, Angelo

doi:10.1016/j.bbrc.2004.04.028

Cited by 77 publications

(72 citation statements)

References 23 publications

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“…TP, when tested with cells in vitro, has been shown to have more potent cellular effects than a-tocopherol itself in terms of inhibition of cell proliferation and regulation of gene expression (11). For instance, the transcriptional inhibition of the scavenger receptor CD36 in human coronary artery smooth muscle cells (HCASMC) after 24 hours incubation with 50 mM a-tocopherol was not significant (3%) while TP, at the same concentration produced more than 40% inhibition (Fig.…”

mentioning

confidence: 98%

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

Negis

Zingg

Ogru³

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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The finding that a-tocopheryl phosphate is present in cells in small amounts, that it can be synthesized and hydrolyzed supports the hypothesis that a-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.

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mentioning

confidence: 98%

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

Negis

Zingg

Ogru³

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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“…Only the treatment with a-tocopheryl phosphate led to a significant reduction of the cellular 20S proteasome activity (Fig. 6), which interestingly inhibited cell proliferation as well (18). At half the concentration (25 mM), the inhibition was still higher for a-tocopheryl phosphate (65 + 14% reduction, n ¼ 4, P 5 0.001) when compared to d-tocopherol (at 50 mM) (60 + 14% reduction, n ¼ 4, P 5 0.001) (Fig.…”

Section: Cellular Proteasome Activity Is Inhibited By A-tocopherylmentioning

confidence: 93%

“…a-Tocopheryl acetate (dl-a-tocopheryl acetate) (Sigma), or a-tocopheryl succinate (d-a-tocopheryl succinate) (Sigma) were dissolved in ethanol, and a-tocopheryl phosphate ((+)-a-tocopheryl phosphate disodium salt) (Sigma) was dissolved in water (18). H 2 O 2 (Fluka) was diluted freshly before each use to give a 1 M stock concentration.…”

Section: Reagentsmentioning

confidence: 99%

“…Phosphate, but not by a-tocopheryl Succinate Several derivatives of a-tocopherol, such as a-tocopheryl succinate and a-tocopheryl phosphate, have been described to have more potent activity on several cellular parameters, including cell proliferation, apoptosis, signal transduction and gene expression (18,42). The higher activity of these analogues could either be explained by acting on novel targets, by increased cellular uptake by tocopherol binding proteins such as TAP (43), or possibly by enhanced recognition of structures that are usually targeted by the natural a-tocopherol.…”

Section: Cellular Proteasome Activity Is Inhibited By A-tocopherylmentioning

confidence: 99%

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

et al. 2007

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SummaryIn THP-1 monocytes, cellular proteasome inhibition by ritonavir or ALLN is associated with increased production of oxidative stress. Both compounds produced comparable amounts of oxidative stress; however, normalization by a-tocopherol occurred solely after inhibition by ritonavir, and not by ALLN. Similar to that, atocopherol could normalize the reduced formation of 3-nitrotyrosine-modified proteins only after ritonavir treatment. In the absence of any proteasome inhibitor, intrinsic cellular proteasome activity was not modulated by a-, b-, and g-tocopherols; however, dtocopherol, a-tocotrienol, and a-tocopheryl phosphate could significantly inhibit cellular proteasome activity and increased the level of p27Kip1 and p53. Since oxidative stress was reduced by atocopherol only after proteasome inhibition by ritonavir and not by ALLN, it is concluded that, in this experimental system, atocopherol does not act as an antioxidant but interferes with the inhibitory effect of ritonavir. IUBMB Life, 59: 771-780, 2007

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“…Furthermore, its dephosphorylation is not efficient. Tocopheryl phosphate modulates the activity of several enzymes; in cell culture, it affects proliferation, signal transduction, and gene expression at concentrations lower than tocopherol (Zingg and coworkers, [41]). In high cholesterol fed rabbits and LDL knockout mice tocopheryl phosphate prevents atherosclerosis at much lower concentrations than tocopherol [40].…”

Section: Phosphorylation: a Way To Activate Vitamin E Signaling And Fmentioning

confidence: 99%

Present trends in vitamin E research

Galli

Azzi

2010

BioFactors

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Abstract.Nearly after one century of research and thousands of publications, the physiological function(s) of vitamin E remain unclear. Available evidence suggests a role in cell homeostasis that occurs through the modulation of specific signaling pathways and genes involved in proliferative, metabolic, inflammatory, and antioxidant pathways. Vitamin E presence in the human body is under close metabolic control so that only a-tocopherol and, to a lower extent, c-tocopherol are retained and delivered to tissues. Other vitamin E forms that are not retained in the body in significant amounts, exhibit responses in vitro that are different form those of a-tocopherol and may include tumor cell specific toxicity and apoptosis. These responses provide a therapeutic potential for these minor forms, either as such or metabolically modified, to produce bioactive metabolites. These cellular effects go beyond the properties of lipophilic antioxidant attributed to a-tocopherol particularly investigated for its alleged protective role in atherosclerosis or other oxidative stress conditions. Understanding signaling and gene expression effects of vitamin E could help assign a physiological role to this vitamin, which will be discussed in this review. Besides vitamin E signaling, attention will be given to tocotrienols as one of the emerging topics in vitamin E research and a critical re-examination of the most recent clinical trials will be provided together with the potential use of vitamin E in disease prevention and therapy.

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Modulation of cell proliferation and gene expression by α-tocopheryl phosphates: relevance to atherosclerosis and inflammation

Cited by 77 publications

References 23 publications

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

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

Present trends in vitamin E research

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