ArticleThe Journal of biological chemistry2014
Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Selenium-enriched foods are more effective at increasing glutathione peroxidase (GPx) activity compared with selenomethionine: a meta-analysis.Nutrients · 2014Pooled it
- Homocysteine Drives Hippocampal Blood-Brain Barrier Disruption and Cognitive Decline Under Chronic Stress via DNA Hypomethylation of Cav1.2.Brain sciences · 2026Article
- Role of hyperhomocysteinemia in atherosclerosis: from bench to bedside.Annals of medicine · 2025Review
- Relationship between plasma homocysteine and clinical grading of varicocele.Asian journal of andrology · 2025Article
- Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis.Redox biology · 2023Article
- RNA methylation and cellular response to oxidative stress-promoting anticancer agents.Cell cycle (Georgetown, Tex.) · 2023Review
- Article
- Plasma inflammatory biomarkers in cerebral small vessel disease: A review.CNS neuroscience & therapeutics · 2023Review
- Genetic and epigenetic factors of arterial hypertension: a bibliometric- and in-silico-based analyses.Frontiers in molecular biosciences · 2023Review
- Mutual effect of homocysteine and uric acid on arterial stiffness and cardiovascular risk in the context of predictive, preventive, and personalized medicine.The EPMA journal · 2022Article
- The role of glutathione peroxidase-1 in health and disease.Free radical biology & medicine · 2022Review
- The Effect of Nutritional Ketosis on Aquaporin Expression in Apolipoprotein E-Deficient Mice: Potential Implications for Energy Homeostasis.Biomedicines · 2022Article
- Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- tRNA Function and Dysregulation in Cancer.Frontiers in cell and developmental biology · 2022Review
- The Effect of tRNAInternational journal of molecular sciences · 2021Article
- A Hypomethylating Ketogenic Diet in Apolipoprotein E-Deficient Mice: A Pilot Study on Vascular Effects and Specific Epigenetic Changes.Nutrients · 2021Article
- Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology.Nutrients · 2021Review
- Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
S-adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.