Modulation of signal transduction by vitamin E

Zingg, Jean‐Marc

doi:10.1016/j.mam.2006.12.009

Cited by 156 publications

(147 citation statements)

References 164 publications

(189 reference statements)

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“…Enzymes inhibited by vitamin E include protein kinases C and B, protein tyrosine kinase, lipoxygenases, mitogen activated protein kinases, phospholipase A2 and cyclooxygenase-2. In contrast, vitamin E has stimulatory effects on protein tyrosine phosphatase and diacylglycerol kinase [228]. Both vitamins C and E have been shown to stimulate the activation of NOS activity and increase .…”

Section: Antioxidantsmentioning

confidence: 98%

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Sousa¹,

Afonso²,

Albino‐Teixeira³

et al. 2012

Lipid Peroxidation

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Section: Antioxidantsmentioning

confidence: 98%

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Sousa¹,

Afonso²,

Albino‐Teixeira³

et al. 2012

Lipid Peroxidation

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“…The biological function of a-tocopherol is made more interesting should we consider the possibility of mechanisms of action independent of antioxidant activity. Indeed, the effect of a-tocopherol on membrane resident proteins and enzymes, signaling cascades, and gene expression, may be related to its contribution to membrane structure and dynamics, and thus modulation of membranedependent signaling mechanisms such as protein and lipid kinases [96][97][98]. We have described here how our work using 2 H-NMR and neutron diffraction will enable a more detailed understanding of how tocopherol behaves when immersed in phospholipid bilayers of increasing polyunsaturation.…”

Section: Is All Of This Relevant For Understanding the Biological Actmentioning

confidence: 99%

The location and behavior of α‐tocopherol in membranes

Atkinson

Harroun

Wassall

et al. 2010

Molecular Nutrition Food Res

173

128

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Vitamin E (a-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the vitamin functions. For example, the very low levels of a-tocopherol reported for whole cell extracts question how this molecule can successfully protect the comparatively enormous quantities of PUFAcontaining phospholipids found in membranes that are highly susceptible to oxidative attack. The contemporary realization that membranes laterally segregate into regions of distinct lipid composition (domains), we propose, provides the answer. We hypothesize a-tocopherol partitions into domains that are enriched in polyunsaturated phospholipids, amplifying the concentration of the vitamin in the place where it is most needed. These highly disordered domains depleted in cholesterol are analogous, but organizationally antithetical, to the wellstudied lipid rafts. We review here the ideas that led to our hypothesis. Experimental evidence in support of the formation of PUFA-rich domains in model membranes is presented, focusing upon docosahexaenoic acid that is the most unsaturated fatty acid commonly found. Physical methodologies are then described to elucidate the nature of the interaction of a-tocopherol with PUFA and to establish that the vitamin and PUFA-containing phospholipids co-localize in non-raft domains.

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“…Intracellular players in signaling expected to be influenced by the interaction between these proteins and vitamin E are numerous (reviewed in [4][5][6][7]) and include kinases such as PKC, Akt/PKB, some members of MAPK family and cell cycle related kinases, and the recently proposed downstream components of the death domain and proteins of the endoplasmic reticulum stress signaling [8]. Tocotrienols have been reported to be ligands of the estrogen receptor b (ERb) [9] that could thus contribute some aspects of vitamin E signaling that will be further discussed later in the section dedicated to tocotrienols.…”

Section: Cellular Effects and Signaling Of Vitamin Ementioning

confidence: 99%

“…Prostate cancer cells (PC3) were also demonstrated to produce high intracellular levels of CEHCs when exposed to tocotrienols [36] and these metabolites were tentatively identified to possess some biological activities resembling those of their vitamer precursors, such as that of antioxidant, anti-inflammatory, and antiproliferative agents, and in the case of c CEHC metabolite also of mild natriuretic factor. These functions occur through signaling effects that CEHC metabolites produce with a close analogy with their vitamin E precursors (reviewed in [7,27,29]). Other than for the final products of vitamin E metabolism CEHCs, signaling effects have been more recently described in the case of long chain metabolites that are present in the circulation and are formed preferentially in some cell lines such as A549 alveolar type II epithelial cells [5].…”

Section: Cellular Effects and Signaling Of Vitamin Ementioning

confidence: 99%

Present trends in vitamin E research

2010

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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 signal transduction by vitamin E

Cited by 156 publications

References 164 publications

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Lipid Peroxidation and Antioxidants in Arterial Hypertension

The location and behavior of α‐tocopherol in membranes

Present trends in vitamin E research

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