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

Sneddon, Alan Arthur; Wu, Huiyun; Farquharson, Andrew J.; Grant, I. S.; Arthur, John R.; Rotondo, Dino; Choe, Sun-Nam; Wahle, Klaus W.J.

doi:10.1016/j.atherosclerosis.2003.08.008

Cited by 94 publications

(60 citation statements)

References 32 publications

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“…This is in agreement with the present study, in which down-regulation was observed in fish fed the feed with highest DHA level. Therefore, transcriptional or post-transcriptional regulation of SEP by LC-PUFA is a possibility, as was shown in vitro for GPX1 and GPX4 (67,68) . Furthermore, the lack of effect in the expression of the other studied SEP may indicate that not all respond in the same way when Se levels are altered, with a hierarchy existing as described previously in mammals (69) .…”

Section: Discussionmentioning

confidence: 99%

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

et al. 2016

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Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

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Section: Discussionmentioning

confidence: 99%

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

et al. 2016

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“…Several mechanisms of transcriptional regulation Maiorino et al 2003) have been suggested for various GPx4-isoforms, but cell activation studies (Kuhn and Borchert 2002;Tramer et al 2002;Sneddon et al 2003) and nonsense-mediated decay experiments (Sun et al 2001;Muller et al 2003) suggested additional post-transcriptional elements. Besides GPx4, other enzymes involved in eicosanoid metabolism such as 15-lipoxygen- …”

Section: Discussionmentioning

confidence: 99%

Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development

Ufer

Wang²,

Fähling³

et al. 2008

Genes Dev.

101

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Phospholipid hydroperoxide glutathione peroxidase (GPx4) is a moonlighting selenoprotein, which has been implicated in basic cell functions such as anti-oxidative defense, apoptosis, and gene expression regulation. GPx4-null mice die in utero at midgestation, and developmental retardation of the brain appears to play a major role. We investigated post-transcriptional mechanisms of GPx4 expression regulation and found that the guanine-rich sequence-binding factor 1 (Grsf1) up-regulates GPx4 expression. Grsf1 binds to a defined target sequence in the 5-untranslated region (UTR) of the mitochondrial GPx4 (m-GPx4) mRNA, up-regulates UTR-dependent reporter gene expression, recruits m-GPx4 mRNA to translationally active polysome fractions, and coimmunoprecipitates with GPx4 mRNA. During embryonic brain development, Grsf1 and m-GPx4 are coexpressed, and functional knockdown (siRNA) of Grsf1 prevents embryonic GPx4 expression. When compared with mock controls, Grsf1 knockdown embryos showed significant signs of developmental retardations that are paralleled by apoptotic alterations (TUNEL staining) and massive lipid peroxidation (isoprostane formation). Overexpression of m-GPx4 prevented the apoptotic alterations in Grsf1-deficient embryos and rescued them from developmental retardation. These data indicate that Grsf1 up-regulates translation of GPx4 mRNA and implicate the two proteins in embryonic brain development.[Keywords: Glutathione peroxidase 4; guanine-rich sequence-binding factor 1; apoptosis; brain development; embryogenesis] Supplemental material is available at http://www.genesdev.org.

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“…Post-transcriptional modifications such as alternative splicing of joint GPx4 mRNA precursors have previously been suggested as factors in GPx4 regulation on the basis of different signaling stimuli or developmental stages Tramer et al, 2002;Borchert et al, 2003;Puglisi et al, 2003;Sneddon et al, 2003). Post-transcriptional mechanisms conferred by the 39-untranslated region that contains the selenocysteine insertion sequence have been studied in more detail.…”

Section: Molecular Mechanisms Of Gpx4 Transcription Regulationmentioning

confidence: 99%

Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function

Savaskan

Ufer

Kühn

et al. 2007

BCHM

114

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Selenoproteins have been recognized as modulators of brain function and signaling. Phospholipid hydroperoxide glutathione peroxidase (GPx4/PHGPx) is a unique member of the selenium-dependent glutathione peroxidases in mammals with a pivotal role in brain development and function. GPx4 exists as a cytosolic, mitochondrial, and nuclear isoform derived from a single gene. In mice, the GPx4 gene is located on chromosome 10 in close proximity to a functional retrotransposome that is expressed under the control of captured regulatory elements. Elucidation of crystallographic data uncovered structural peculiarities of GPx4 that provide the molecular basis for its unique enzymatic properties and substrate specificity. Monomeric GPx4 is multifunctional: it acts as a reducing enzyme of peroxidized phospholipids and thiols and as a structural protein. Transcriptional regulation of the different GPx4 isoforms requires several isoform-specific cis-regulatory sequences and trans-activating factors. Cytosolic and mitochondrial GPx4 are the major isoforms exclusively expressed by neurons in the developing brain. In stark contrast, following brain trauma, GPx4 is specifically upregulated in non-neuronal cells, i.e., reactive astrocytes. Molecular approaches to genetic modification in mice have revealed an essential and isoform-specific function for GPx4 in development and disease. Here we review recent findings on GPx4 with emphasis on its molecular structure and function and consider potential mechanisms that underlie neural development and neuropathological conditions.

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

Cited by 94 publications

References 32 publications

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salarL.) fed diets with graded levels of plant ingredients

Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development

Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function

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