Biomedical subjects

John R Arthur

Publications and source records attributed to John R Arthur.

18 recordsLinked to original sources

PubMed2006

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. Parallel cultures of selenium- and sulforaphane-treated cells were exposed to tertiary butyl hydroperoxide (t-BuOOH; 0-500 microM) for 20 h, and cell integrity was determined by the percentage of lactate dehydrogenase retained by the cellular layer. RESULTS: Selenite treatment increased the concentration of TR-1 (1.6 +/- 0.17 fold, P < 0.05), GPX-1 activity (8.2 +/- 1.08 fold, P < 0.001), and GPX-4 activity (3.1 +/- 0.25 fold, P < 0.001). Sulforaphane induced TR-1 expression in selenium-deficient cells (1.83 +/- 0.11 fold, P < 0.001) and selenium-supplemented cells (2.90 +/- 0.17 fold, P < 0.001) but had no inductive effect on GPX-1 or GPX-4. The combination of selenite and sulforaphane produced an increase in TR-1 expression that was significantly greater (P < 0.001) than that achieved when each agent was added alone. Selenium and sulforaphane acted in a synergistic manner to protect cells from damage caused by t-BuOOH. The susceptibility of cells to damage by t-BuOOH increased in this order: control > sulforaphane > selenite > selenite + sulforaphane (P < 0.0001). CONCLUSION: In endothelial cells, sulforaphane increases TR-1 but not GPX-1 and GPX-4 and in doing so confers protection against oxidative damage induced by lipid hydroperoxides. The results highlight the potential important role of TR-1 over the GPXs in protecting endothelial cells from oxidative cell damage. We also suggest that our results indicate a potential beneficial role for sulforaphane in protecting the vascular endothelium from oxidative damage.

Anticarcinogenic Agents↗

PubMed2006

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. About 47% of the total cell enzyme activity was found in the membrane fractions, 29% in the mitochondria and 23% in the cytosol fractions. The same subcellular distribution of GPx-4 protein was demonstrated in resting platelets. This distribution data was further established by confocal microscopy. Of major potential biological significance, this distribution changed when platelets were activated. Confocal immunofluorescence microscopy localized mainly GPx-4 to membranes in contrast to cytoplasm in the resting cells. Based on these results we propose that cytoplasmic GPx-4 could be moved to the membrane for protection during platelet activation. This enzyme would then be important to maintain the integrity of platelet function in vascular system stressed by oxidative reactions.

Blood Platelets↗

PubMed2006

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). CLA inhibited the binding of both THP-1 and isolated human peripheral blood monocytes to HUVEC by up to 40% with the CLA t10,c12 isomer suppressing adhesion dose-dependently. Investigation into the mechanism involved demonstrated that with IL-1beta, VCAM-1 and ICAM-1 levels and pro-inflammatory cytokine expression were largely unaffected by CLA. Through the use of PAF receptor antagonists and PAF synthesis inhibitors, CLA was shown to inhibit cytokine-induced binding by suppressing PAF production. Direct assay of PAF levels confirmed this result. We conclude that endothelial-generated PAF plays a central role in cytokine-induced monocyte adherence to endothelium and that the anti-inflammatory action of PUFAs such as CLA in suppressing monocyte-endothelial interaction is mediated through attenuation of pro-inflammatory phospholipids such as PAF.

Cell Adhesion↗

PubMed2006

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.

Absorption↗

PubMed2005

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. Semi-quantitative PCR performed previously demonstrated RNA expression of Gpx1 and Gpx2 in proximal, transverse and distal colon. Mapping the distribution throughout the entire colon has revealed specific, novel sites of glutathione peroxidase expression in colon lymphatic tissue. In situ hybridisation and immunohistochemistry confirmed micro-anatomical location of Gpx1 within lymphatic tissue and the lamina propria, sub-mucosa, muscularis and serosa, but not the lumenal epithelium. In situ hybridisation and immunohistochemistry were consistent with reports of microanatomical location of Gpx2 in the lumenal epithelium. Novel sites of Gpx2 expression were also observed in lymphatic tissue. Immunolocalisation in the vicinity of aberrant crypt foci was also examined to further investigate the link between glutathione peroxidases and colon cancer. This did not reveal significant abnormalities, nor did measurement of cytosolic glutathione peroxidase activity or gene expression in colon tissue from rats treated with the colontropic chemical, 1,2-dimethylhydrazine. These results support the potential for Gpx1 and Gpx2 redundancy in lymphatic tissue, but not in epithelial cells of the colon crypt or in the lamina propria, sub-mucosa, muscularis or serosa.

Animals↗

PubMed2005

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. The mechanism of action is unclear although salicylic acid, the main metabolite of aspirin, has been shown to decrease the synthesis of pro-inflammatory and potentially neo-plastic prostaglandins. Salicylic acid is found in significant quantities in a plant-based diet. However, in plants salicylic acid is also reported to modulate the expression of numerous enzymes with antioxidant activity. The aim of this study was to assess whether salicylic acid can modulate pro-cancerous biological pathways in the colon. Oxidative stress, prostaglandins and cytosolic glutathione peroxidase (cyGPX) were analysed in proximal, transverse and distal colon from a rat model of diet-induced oxidative stress. Elevated plasma pyruvate kinase activity (1293+/-206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4+/-0.84 nM MDA/mg protein; transverse 6.9+/-0.97 nM MDA/mg protein; distal 5.2+/-0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546+/-43 U/ml; salicylic acid proximal 3.6+/-0.39 nM MDA/mg protein; transverse 4.5+/-0.61 nM MDA/mg protein; distal 4.4+/-0.27 nM MDA/mg protein). Reductions in oxidative stress and prostaglandin production on supplementation with salicylic acid were associated with an elevation in glutathione peroxidase activity (Vitamin E deficient proximal 0.056+/-0.013 U/mg protein; transverse 0.073+/-0.008 U/mg protein; distal 0.088+/-0.010 U/mg protein; Vitamin E deficient with salicylic acid proximal 0.17+/-0.01 U/mg protein; transverse 0.23+/-0.016 U/mg protein; distal 0.16+/-0.020 U/mg protein). Gpx1 and Gpx2 gene transcripts were not elevated in association with increased activity of the soluble glutathione peroxidase activity. Glutathione peroxidases are key antioxidant enzymes, catalysing the decomposition of potentially toxic lipid peroxides. Gpx activity and regulation of Gpx gene transcription has been shown previously to be complex with activity not necessarily mirrored by a corresponding elevation in gene transcription. By supplementing the diet of Vitamin E deficient rats with salicylic acid (1 g/kg diet), this study assessed effects of salicylic acid on cytosolic glutathione peroxidase activity in the colon. The ability of salicylic acid to modulate antioxidant enzymes in colon tissue may be an important mechanism in inhibiting colon cancer development.

Animals↗

PubMed2005

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. In this study, a CHO-K1 cell line continuously overexpressing MT (MToex) was developed in order to evaluate the relative protection afforded by MT against different toxic agents. Cadmium was used as a positive control and, as expected, the MToex cells were more than 13-fold more resistant to the effects of cadmium chloride than were wild-type (WT) cells using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay (IC50 values of 10 and 132 microM for WT and MToex cells, respectively). In contrast, overexpression of MT afforded no protection against mercuric chloride, staurosporine and hydrogen peroxide (IC50 values of about 50, 11 and 925 microM, respectively). Cd and Hg uptake by MToex and WT cells exposed to 1-10 microM of metal chloride was similar and yet a significant amount of these metals was associated with the cytosol MT fraction in the MToex cells but not in the WT cells. From this study it can be concluded that while MT overexpression protects against Cd toxicity, it has no influence on Hg, staurosporine or hydrogen peroxide toxicity and it is proposed that this reflects mechanistic differences of toxicity or depletion of labile intracellular zinc by the presence of excess binding ligand in the form of MT.

Animals↗

PubMed2005

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. Protein profiles were assessed in soluble and insoluble fractions prepared from distal colon of rats treated with the colonotropic carcinogen, dimethylhydrazine. Alterations in protein profiles were associated with the presence of aberrant crypt foci, hyperplasia and dysplasia, microanatomical changes, and metabolic changes in rat colon. These changes may have a potential role in the identification of pre-pathological features preceding colon tumorigenesis.

Animals↗

PubMed2005

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. Se is also involved in cell growth, apoptosis and modifying the action of cell signalling systems and transcription factors. During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage. Thyroidal D1 in rats and both D1 and D2 in humans are also up-regulated to increase the production of bioactive 3,5,3'-tri-iodothyronine (T3). In the basal state, GPX3 is secreted into the follicular lumen where it may down-regulate thyroid hormone synthesis by decreasing hydrogen peroxide concentrations. The deiodinases are present in most tissues and provide a mechanism whereby individual tissues may control their exposure to T3. Se is also able to modify the immune response in patients with autoimmune thyroiditis. Low sperm production and poor sperm quality are consistent features of Se-deficient animals. The pivotal link between Se, sperm quality and male fertility is GPX4 since the enzyme is essential to allow the production of the correct architecture of the midpiece of spermatozoa. Se also has insulin-mimetic properties, an effect that is probably brought about by stimulating the tyrosine kinases involved in the insulin signalling cascade. Furthermore, in the diabetic rat, Se not only restores glycaemic control but it also prevents or alleviates the adverse effects that diabetes has on cardiac, renal and platelet function.

Animals↗

PubMed2004

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 1.11.1.12) (GPx-4) isolated from rat testes and the second one is the cytosolic glutathione peroxidase (EC 1.11.1.9) (GPx-1) from bovine erythrocytes. Injected in the subphase buffer of a Langmuir trough, GPx-4 was able to adsorb quickly at the air-water interface whereas the GPx-1 was not. Then, the protein interaction with phospholipid monolayers was explored. Indeed, a monolayer of phospholipids containing a different number of polyunsaturated fatty acyl chains was prepared at the air-water interface. Under each kind of monolayer, the protein solution was injected and its adsorption was visualized by the measurement of successive pressure-area isotherms. We have, then, determined the molecular area increase due to the protein adsorption. It was found that the GPx-4 is adsorbed in each kind of monolayer tested whereas no molecular area increase was detected with the GPx-1. This indicates that the GPx-4 has a higher affinity for the interface, recovered or not by lipids, than the GPx-1. Moreover, the GPx-4 presents a different affinity for the phospholipid monolayers depending on the number of polyunsaturated fatty acyl chains.

Adsorption↗

PubMed2004

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. DESIGN: Twenty-two adult UK subjects with relatively low plasma selenium concentrations (<1.2 micromol/L, approximately 60% of those screened) received 50 or 100 microg Se (as sodium selenite) or placebo daily for 15 wk in a double-blind study. All subjects received an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable (74)Se intravenously 3 wk later. RESULTS: Selenium supplementation increased plasma selenium concentrations, the body exchangeable selenium pool (measured by using (74)Se), and lymphocyte phospholipid and cytosolic glutathione peroxidase activities. Selenium supplements augmented the cellular immune response through an increased production of interferon gamma and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells. Humoral immune responses were unaffected. Selenium-supplemented subjects also showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase-polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations. CONCLUSIONS: The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral handling. They also suggest that the additional 100 microg Se/d may be insufficient to support optimal function.

Adult↗

PubMed2003

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. In human umbilical vein endothelial cells (HUVEC), GPx4 mRNA levels and activity were increased optimally by 114 nM selenium (as sodium selenite). Docosahexaenoic acid (DHA) and conjugated linoleic acid (CLA) further increased mRNA levels whereas arachidonic acid (ARA) had no effect; enzyme activity was decreased by DHA, was unaffected by CLA or was increased by ARA. GPx4 protein levels increased with selenium, ARA and DHA addition but not with CLA. Interleukin-1beta (IL-1beta) increased GPx4 mRNA, protein and activity whereas TNFalpha at 1 ng/ml increased activity while at 3 ng/ml it reduced activity and mRNA. Conversely, alpha-tocopherol reduced mRNA levels without affecting activity. These results indicate that lipids, cytokines and antioxidants modulate GPx4 in a complex manner that in the presence of adequate selenium, may favour protection against potentially proatherogenic processes.

Antioxidants↗

PubMed2003

Selenium supplementation: does soil supplementation help and why?

There are now concerns that dietary Se intake is inadequate for the population in the UK and parts of Europe. Many different methods can be proposed to deal with this problem. Experience from Finland suggests that the addition of Se to fertiliser is a safe and effective means of increasing the intake of the micronutrient in the human population. However, careful consideration needs to be given to the potential consequences of increasing Se intake. It is important to understand the biochemical and physiological changes that may occur with any increase in Se intake within the UK population. Se is an essential component of at least twenty functional proteins within mammals. These proteins are essential for a range of metabolic functions, including antioxidant activity, thyroid hormone synthesis and immune function. Thus, any increase in Se intake has the potential to influence in a wide range of factors that may impinge on the incidence of chronic disease. Treatment of soil with Se-supplemented fertiliser will certainly increase total Se in food products derived from areas where this treatment is in place. Consumption of such foods will increase Se status in many populations where the existing intake does not meet requirements. If the increases in Se intake are not toxic the overall consequences have the potential to be beneficial.

Animals↗

PubMed2003

Selenium in the immune system.

Selenium as an essential component of selenocysteine-containing protein is involved in most aspects of cell biochemistry and function. As such, there is much potential for selenium to influence the immune system. For example, the antioxidant glutathione peroxidases are likely to protect neutrophils from oxygen-derived radicals that are produced to kill ingested foreign organisms. When the functions of all selenoproteins are described, only then will it be possible to fully understand their role in maintaining optimal immune function.

Animals↗

PubMed2003

Selenoenzyme activities in selenium- and iodine-deficient sheep.

This study was conducted to evaluate the effects of single and combined deficiencies of selenium and iodine on selenoenzyme activities in sheep. Twenty-four male lambs were assigned to one of four semisynthetic diets: combined deficient A (Se-I), Se-deficient B (Se-I+), I-deficient C (Se+I-), and basal diet D (Se+I+). Thyroid hormones (T3, T4), thyroid stimulating hormone (TSH), and inorganic iodine (PII) were determined in plasma. Selenium and glutathione peroxidase activity (GSH-Px) were determined in erythrocytes, and tissue samples, including the thyroid, liver, kidney, and brain, were taken for selenoenzyme analysis. Plasma T3, T4, and TSH concentrations were similar in all groups. Type I deiodinase (ID-I) activity in liver and kidney remained unchanged in Se or I deficiency. In contrast, hepatic ID-I activity was increased by 70% in combined Se-I deficiency. Thyroidal cystolic GSHPx (c-GSH-Px) and phospholipid GSH-Px (ph-GSH-Px) activities remained constant in both Se-deficient groups, whereas thyroidal c-GSH-Px activity increased (57%) in I deficiency. Type II deiodinase (ID-II) activity was not detectable in the cerebrum and cerebellum, whereas cerebellum Type III deiodinase (ID-III) activity was decreased in I deficiency and combined Se-I deficiencies. The results of the present study support a sensitive interaction between Se and I deficiencies in sheep thyroid and brain. Furthermore, the lack of thyroidal ID-I activity, the preservation of the thyroidal antioxidant enzymes, and the increases in hepatic ID-I indicate that a compensatory mechanism(s) works toward retaining plasma T3 levels, mostly by de novo synthesis of T3 and peripheral deiodination of T4 in Se- and I-deficient sheep.

Animals↗

PubMed2002

Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides.

The human endothelial cell line EAhy926 was used to determine the importance of selenium in preventing oxidative damage induced by tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density lipoprotein (LDLox). In cells grown in a low selenium medium, tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555 mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after 20 h. No significant cell kill was achieved by these agents if cells were pre-incubated for 48 h with 40 nM sodium selenite, a concentration that maximally induced the activities of cytoplasmic glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR; 3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold thioglucose (GTG) (a concentration that inhibited 25% of TR activity but had no inhibitory effect on cyGPX or PHGPX activity) were significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50) 110 microM) than selenium-deficient cells (LC(50) 175 microM). This was also the case for LDLox. In contrast, cells pre-treated with 40 nM selenite prior to exposure to GTG were significantly more resistant to damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment with GTG or selenite had no significant effect on intracellular total glutathione concentrations. These results suggest that selenium supplementation, acting through induction of TR and GPX, has the potential to protect the human endothelium from oxidative damage.

Aurothioglucose↗

PubMed2002

Selenium and the regulation of cell signaling, growth, and survival: molecular and mechanistic aspects.

In the past 30 years, it has been recognized that dietary selenium (Se) is essential for the normal function of many of the systems of the body. Furthermore, low Se intake can have deleterious effects on several aspects of human and animal health. The importance of Se is characterized in its role as a constituent of several key antioxidant and redox enzyme families. Most of the effects of Se are probably mediated by selenoproteins, which have the micronutrient covalently incorporated into the protein. The purpose of this review is to examine basic mechanisms by which Se regulates cell growth, gene transcription, cell signaling, and cell death. We start with the historical background to Se. The synthesis and function of selenoproteins are described, followed by details of the dietary sources of Se and Se status in different parts of the world, together with the clinical effects of Se deficiency and toxicity. We consider some aspects of the molecular mechanisms by which Se modulates cell growth, intracellular signaling, and gene transcription.

Animals↗

PubMedDate not supplied

A novel single nucleotide polymorphism in the 3' untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism.

Selenium (Se) is an essential micronutrient for human health. The biological roles of the essential micronutrient Se are attributed to its presence in a range of 20-30 selenoproteins including the cytosolic and phospholipid hydroperoxide glutathione peroxidases (GPX1 and GPX4). It has been suggested that GPX4 may play a role in regulation of leukotriene biosynthesis and thus inflammation. In eukaryotes Se is incorporated into selenoproteins as the amino acid selenocysteine in a process requiring a stem-loop within the 3' untranslated region (3'UTR) of the mRNA. In this study the region of the GPX4 gene corresponding to the 3'UTR was scanned for mutations in a group of 66 volunteers. The data show a T/C variant at position 718. The distribution of this SNP in our population was 34% CC, 25% TT and 41% TC; i.e., it is in Hardy-Weinberg equilibrium. Individuals of different genotypes exhibited significant differences in the levels of lymphocyte 5-lipoxygenase total products, with C718 showing increased levels of those products compared to T718 and T/C718 (36% and 44% increases, respectively). The data suggest that the SNP718 that we have identified has functional effects and support the hypothesis that GPX4 plays a regulatory role in leukotriene biosynthesis.

3' Untranslated Regions↗