Vitamin E, antioxidant and nothing more.

Oxidative stress and cancer: an overview.

The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

https://www.liebertpub.com/doi/pdf/10.1089/ars.2007.1528

From selenium to selenoproteins: Synthesis, identity, and their role in human health

This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

Selenium in human health and disease.

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have been attributed to their intrinsic reducing capabilities. They may also offer indirect protection by activating endogenous defense systems and by modulating cellular signaling processes such as nuclear factor-kappa B (NF-κB) activation, activator protein-1(AP-1) DNA binding, glutathione biosynthesis, phosphoinositide 3 (PI3)-kinase/protein kinase B (Akt) pathway, mitogen-activated protein kinase (MAPK) proteins [extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinase (JNK) and P38 ] activation, and the translocation into the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2). This paper covers the most recent literature on the subject, and describes the biological mechanisms of action and protective effects of dietary polyphenols.

/pdf/dietary-polyphenols-and-their-biological-significance-216gryq5fb.pdf

Dietary Polyphenols and Their Biological Significance

The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., “antioxidants” known to activate the “antioxidant response element” (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx.

The GI-GPx Gene Is a Target for Nrf2

Vitamin E activates gene expression via the pregnane X receptor.

The metabolism of alpha- and gamma-tocotrienol was investigated in HepG2 cells. Metabolites were identified by HPLC and gas chromatography/mass spectrometry. gamma-Tocotrienol was degraded to gamma-CEHC (carboxyethyl hydroxychroman), gamma-CMBHC (carboxymethylbutyl hydroxychroman), gamma-CMHenHC (carboxymethylhexenyl hydroxychroman), gamma-CDMOenHC (carboxydimethyloctenyl hydroxychroman) and gamma-CDMD(en)(2)HC (carboxydimethyldecadienyl hydroxychroman). alpha-Tocotrienol yielded alpha-CEHC, alpha-CMBHC, alpha-CMHenHC and alpha-CDMOenHC, whereas alpha-CDMD(en)(2)HC could not be detected. These findings demonstrate that the trienols are metabolized essentially like tocopherols, i.e., by omega-oxidation followed by beta-oxidation of the side chain. The failure to detect CMBHC with the original double bond in the side chain reveals that auxiliary enzymes are involved, as in the metabolism of unsaturated fatty acids. CMBHC were the most abundant metabolites obtained from the tocotrienols as well as from alpha-tocopherol. Quantitatively, the tocotrienols were degraded to a larger extent than their counterparts with saturated side chains. The pronounced quantitative differences in the metabolism between individual tocopherols as well as between tocotrienols and tocopherols in vitro suggest a corresponding lack of equivalence in vivo.

/pdf/identities-and-differences-in-the-metabolism-of-tocotrienols-1wli68bd2i.pdf

Dirk Kluth

Papers

The GI-GPx Gene Is a Target for Nrf2

Vitamin E activates gene expression via the pregnane X receptor.

Identities and Differences in the Metabolism of Tocotrienols and Tocopherols in HepG2 Cells

Modulation of pregnane X receptor- and electrophile responsive element-mediated gene expression by dietary polyphenolic compounds.

Modulation of Cyp3a11 mRNA expression by alpha-tocopherol but not gamma-tocotrienol in mice.