The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: interaction with selenium and fatty acids.

Scope: Selenium (Se) is incorporated into selenoproteins as selenocysteine, which requires structures in the 3'-untranslated region (3'-UTR) of selenoprotein mRNAs. The functional consequences of a single nucleotide polymorphism (SNP) within the 3'-UTR of the selenoprotein GPX4 gene (GPX4c718t) was assessed in human umbilical vein endothelial cells (HUVECs) and monocytes from human volunteers.

Methods And Results: HUVEC and monocytes homozygous for the T- or C-variant of the GPX4c718t SNP were assessed for monocyte-endothelial cell adhesion, expression of VCAM-1 and sensitivity to oxidative challenge.

High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci.

Background: Obesity is associated with an increased risk of colon cancer. High-fat diets that lead to obesity may be a contributing factor, but the mechanisms are unknown.

Aims: This study examines susceptibility to azoxymethane (AOM)-induced precancerous lesions in mice in response to consumption of either a low or a high-fat diet and associated molecular changes in the liver and colon.

Leptin up-regulates pro-inflammatory cytokines in discrete cells within mouse colon.

Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues.

Aqua regia extractable selenium concentrations of some Scottish topsoils measured by ICP-MS and the relationship with mineral and organic soil components.

Background: To provide information concerning the geographical distribution of selenium (Se) in the soils of Scotland, we analysed 47 arable soils selected on the basis of their parent rock, which were expected to have relatively high, low or unclassified Se concentrations. To investigate relationships between the actual minerals in the soils and the aqua regia extractable Se concentration of the soil, soil minerals were quantified by X-ray diffraction.

Results: The aqua regia extractable Se concentrations of the soils were between 0.

Selenoenzymes, laboratory parameters, and trace elements in different types of thyroid tumor.

This study was performed to investigate selenoenzyme activities and trace element concentrations in thyroid tissues, with reference to other parameters routinely used to characterize thyroid function. This was to reveal relevant parameters as possible additional markers of tumor grade, clinical course, and prognosis of thyroid disorders. The tissue samples were obtained during surgical treatment (total or near total thyroidectomy) of 122 patients with different types of thyroid tumor.

Modulation of thioredoxin reductase-2 expression in EAhy926 cells: implications for endothelial selenoprotein hierarchy.

Background: We examined the expression of the mitochondrial selenoenzyme TrxR2 in the endothelial cell line EAhy926 under conditions known to modify its cytoplasmic counterpart TrxR1.

Methods: Cells were cultured with varying concentrations of selenite, sulforaphane or the Ca2+ ionophore A23187 for 72-h, prior to assay of TrxR concentration and activity. Further cultures underwent prolonged (7-day) Se-depletion before selenoprotein measurement.

Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status.

Selenium (Se), a dietary trace metal essential for human health, is incorporated into selenoproteins as selenocysteine. Selenoprotein P (SePP), the major plasma selenoprotein, has both transport and antioxidant functions. In humans, it exists in plasma as two isoforms of approximately 50 and 60 kDa.

Differential effects of doses and forms of dietary selenium on immune cell numbers in the skin of ultraviolet-irradiated and unirradiated mice.

The effect of three different doses of dietary L-selenomethionine (SM) and sodium selenite (SS) on skin selenium (Se) content, glutathione peroxidase (GPx) activity, Langerhans cell (LC) and mast cell numbers in ultraviolet radiation-B (UVB)-irradiated and unirradiated C3H/HeN mice was determined. After weaning, groups of mice were given Se-deficient, Se-adequate, or Se-high diets. Six weeks later, some animals in each group were exposed to a single UVB dose (acute), while others were exposed three times weekly for the following 40 weeks (chronic).

Functional effects of a common single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene: interaction with sex.

Background: Selenium is essential for health in humans. Selenium is present as selenocysteine in selenoproteins such as the glutathione peroxidases (GPx). Selenocysteine incorporation requires specific structures in the 3'untranslated region (3'UTR) of selenoprotein mRNAs.

Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in APOE-/- mice.

We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe-/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p < 0.05), though Picual olive oil significantly decreased plasma triglycerides (p < 0.

Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine.

Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues.

Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study).

Selenium (Se), a micronutrient essential for human health, is incorporated into at least 25 selenoproteins including selenoprotein P (SePP), which transports Se within the body. This research identified two single nucleotide polymorphisms (SNPs) in the SePP gene, one in the coding region (position 24731, causing an Ala to Thr change) and one in the 3'untranslated region (position 25191). Their frequency was similar in Caucasian, Chinese, and South Asian populations.

Lack of effect of oral selenite on p53 associated gene expression during TL01 therapy of psoriasis patients.

Selenium (Se) has protective properties against ultraviolet (UV)-induced changes in skin cells in vitro but little is known about such activity in human subjects. In the present study, seven patients with psoriasis ingested 400 microg of sodium selenite daily during a 4 week course of whole-body narrow-band UVB (TL01) therapy while six more psoriasis patients, similarly irradiated, ingested a placebo. Skin biopsies, collected at the start and end of the phototherapy were analysed for phosphorylated p53, Fas, Bcl-2, Bax and oxidized guaninosine, and for numbers of Langerhans and sunburn cells.

Selenium and sulforaphane modify the expression of selenoenzymes in the human endothelial cell line EAhy926 and protect cells from oxidative damage.

Objective: We examined the ability of sulforaphane and selenium to modify the expression of thioredoxin reductase (TR-1) and the glutathione peroxidases (GPX-1 and GPX-4) in EAhy926 cells. The effectiveness of these agents to protect cells against peroxidative damage was also assessed.

Methods: EAhy926 cells were supplemented with 40 nM of selenite and/or sulforaphane (10 microM) for 72 h and the expression of TR-1, GPX-1, and GPX-4 was assessed.

Functional markers of selenium status: UK Food Standards Agency workshop report.

The workshop was organised to discuss the validity and limitations of existing functional markers of Se status in human subjects and to identify future research priorities in this area. Studies presented as part of this workshop investigated: the bioavailability of Se from different dietary sources; potential functional markers of Se status; individual variation in response to Se; the effect of marginal Se status on immune function. The workshop highlighted the need to define the relationship between functional markers of Se status and health outcomes.

Phospholipid-hydroperoxide glutathione peroxidase (GPx-4) localization in resting platelets, and compartmental change during platelet activation.

Seleno-glutathione peroxidases are an important family of antioxidant enzymes, that include the phospholipid hydroperoxide glutathione peroxidase (GPx-4), an enzyme that reduces lipid hydroperoxides in membranes. The essential characteristics of platelet GPx-4 were found to be the same as the GPx-4 from other tissues. To explore the subcellular expression of GPx-4 in human platelets, we first investigated both its activity and localization in subcellular fractions.

Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid.

Monocyte-endothelium interaction is key to many acute and chronic inflammatory diseases. We have investigated the factors regulating monocyte attachment to cytokine-activated human umbilical vein endothelial cells (HUVEC) and the modulatory effect of the polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA) in this process. Both TNF-alpha and IL-1beta induced HUVEC platelet-activating factor (PAF) production and PAF was required for subsequent firm THP-1 monocyte adhesion since it was inhibited by both PAF receptor antagonists (BN-52021 or CV-6209) and a PAF synthesis inhibitor (sanguinarine).

Novel sites of cytosolic glutathione peroxidase expression in colon.

Glutathione peroxidases (Gpx) are important moderators of oxidative stress that is implicated in the pathogenesis of numerous diseases including colon cancer. Previous studies report limited examinations of cytosolic glutathione peroxidase location of expression in colon tissue. This study reports evidence of both common sites of Gpx1 and Gpx2 expression in rat colon and sites that are exclusive to each isoform.

Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon.

Oxidative stress is a characteristic of cancerous colon tissue and inflammatory bowel diseases that increase colon cancer risk. Epidemiological evidence supports a protective effect of plant-derived compounds. Aspirin is also protective against colon cancer.

Metallothionein overexpression and resistance to toxic stress.

Metallothionein (MT) protects against the harmful effects of a wide spectrum of stress factors. The most studied of these factors is cadmium, whose toxicity is reduced on sequestration by MT. However, there is poorer consensus in the literature about protection afforded by MT against stressors other than cadmium.

A proteomics approach to identify changes in protein profiles in pre-cancerous colon.

The development of colon cancer is characterised by alterations in multiple genetic and epigenetic pathways in colon tissue leading ultimately to deregulation of colon epithelial cells. Early detection is an important factor in decreasing colon cancer deaths. Proteomic techniques were used to identify potential early markers in colon tissue exhibiting pre-cancerous activity that may characterise pathological changes in a chemically induced colon cancer rat model.

Selenium and endocrine systems.

The trace element selenium (Se) is capable of exerting multiple actions on endocrine systems by modifying the expression of at least 30 selenoproteins, many of which have clearly defined functions. Well-characterized selenoenzymes are the families of glutathione peroxidases (GPXs), thioredoxin reductases (TRs) and iodothyronine deiodinases (Ds). These selenoenzymes are capable of modifying cell function by acting as antioxidants and modifying redox status and thyroid hormone metabolism.

Adsorption of a phospholipid-hydroperoxide glutathione peroxidase into phospholipid monolayers at the air-water interface.

The interfacial behavior differences of two glutathione peroxidase isoforms have been investigated. The first isoform is the phospholipid-hydroperoxide glutathione peroxidase (EC 1.11.

An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status.

Background: Dietary selenium intakes in many countries, including the United Kingdom, are lower than international recommendations. No functional consequences of these lower intakes have been recognized, although experimental studies suggest that they might contribute to reduced immune function, increased cancer incidence, and increased susceptibility to viral disease.

Objective: The objective was to assess whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus: live attenuated polio vaccine.

Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants.

Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid peroxidation. Peroxidation of lipids has been implicated in a number of pathophysiological processes, including inflammation and atherogenesis. We investigated the relative positive and negative effects of specific polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity and gene expression of the selenium-dependant redox enzyme GPx4.