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

Autor: Alan A. Sneddon, Shabina Bashir, John E. Hesketh, Fergus Nicol, John R. Arthur, Lynne K. Crosley
Rok vydání: 2013
Předmět:
Adult
Male
Vascular Cell Adhesion Molecule-1
Single-nucleotide polymorphism
Glutathione peroxidase 4
030204 cardiovascular system & hematology
Biology
GPX4
Monocyte
Polymorphism
Single Nucleotide
Umbilical vein
Monocytes
Endothelial
03 medical and health sciences
Selenium
0302 clinical medicine
Glutathione Peroxidase GPX1
medicine
Cell Adhesion
Human Umbilical Vein Endothelial Cells
Humans
3' Untranslated Regions
Research Articles
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Glutathione Peroxidase
Arachidonic Acid
Lipid peroxide
Glutathione peroxidase
Fatty Acids
Homozygote
Osteoprotegerin
Endothelial Cells
Middle Aged
Phospholipid Hydroperoxide Glutathione Peroxidase
Molecular biology
Single nucleotide polymorphism
Endothelial stem cell
medicine.anatomical_structure
Biochemistry
chemistry
Fatty Acids
Unsaturated
Selenoprotein
Endothelium
Vascular
Lipid Peroxidation
Food Science
Biotechnology
Zdroj: Molecular Nutrition & Food Research
ISSN: 1613-4133
Popis: 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. Interaction of the SNP with Se and different PUFA and effects on selenoprotein expression were also investigated. HUVEC and monocytes homozygous for the T-variant showed elevated adhesion levels compared to cells of the C-variant. This effect was modified by Se and PUFA. HUVEC homozygous for the T-variant showed elevated levels of VCAM-1 protein in the presence of arachidonic acid, were more sensitive to oxidative challenge and showed Se-dependant changes in lipid peroxide levels and expression of additional selenoproteins. Conclusion These findings demonstrate functional effects of the GPX4c718t SNP in endothelial cells and may suggest that individuals with the TT genotype have impaired endothelial function and are at greater risk of vascular disease compared to individuals with the CC genotype.
Databáze: OpenAIRE
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