ArticleCirculation research2008
Tumor necrosis factor-alpha downregulates endothelial nitric oxide synthase mRNA stability via translation elongation factor 1-alpha 1.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 150 citations in OpenAlex.
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- C-C Motif chemokine receptor-2 blockade ameliorates pulmonary hypertension in rats and synergizes with a pulmonary vasodilator.Cardiovascular research · 2025Article
- The Crosstalk Between Endothelial Cells, Smooth Muscle Cells, and Macrophages in Atherosclerosis.International journal of molecular sciences · 2025Review
- The Co-Existence of Hypovitaminosis D and Diabetes Mellitus Triples the Incidence of Severe Coronary Artery Disease in Women.Journal of clinical medicine · 2024Article
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
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- New Therapeutics for Heart Failure Worsening: Focus on Vericiguat.Journal of clinical medicine · 2024Review
- Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.International journal of molecular sciences · 2024Article
- Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.The Journal of clinical investigation · 2024Article
- Global Transcriptome Analysis Reveals Distinct Phases of the Endothelial Response to TNF.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.The Journal of clinical investigation · 2023Article
- Defective Bile Acid Signaling Promotes Vascular Dysfunction, Supporting a Role for G-Protein Bile Acid Receptor 1/Farnesoid X Receptor Agonism and Statins in the Treatment of Nonalcoholic Fatty Liver Disease.Journal of the American Heart Association · 2023Article
- Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2023Article
- Neuraminidase inhibition improves endothelial function in diabetic mice.American journal of physiology. Heart and circulatory physiology · 2023Article
- The Impacts of Animal-Based Diets in Cardiovascular Disease Development: A Cellular and Physiological Overview.Journal of cardiovascular development and disease · 2023Review
- Article
- Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options.Biomedicines · 2022Review
- The Inflammatory Pattern of Chronic Limb-Threatening Ischemia in Muscles: The TNF-α Hypothesis.Biomedicines · 2022Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Endothelium-derived nitric oxide (NO) is an important regulator of vascular function. NO is produced by endothelial NO synthase (eNOS), whose expression is downregulated by tumor necrosis factor (TNF)-alpha at the posttranscriptional level. To elucidate the molecular basis of TNF-alpha-mediated eNOS mRNA instability, eNOS 3' untranslated region (3'-UTR) binding proteins were purified by RNA affinity chromatography from cytosolic fractions of TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs). The formation of 3'-UTR ribonucleoprotein complexes, with molecular weight of 52 and 57 kDa, was increased by TNF-alpha. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of the 52-kDa protein identified 3 peptides that comprise the peptide sequence of translation elongation factor 1-alpha 1 (eEF1A1). In HUVECs, TNF-alpha rapidly increased eEF1A1 expression, which is maximal after 1 hour and persists for up to 48 hours. RNA gel mobility-shift and UV cross-linking assays indicated that recombinant glutathione S-transferase-eEF1A1 fusion protein specifically binds to a UC-rich sequence in the 3'-UTR of eNOS mRNA. In addition, the domain III of eEF1A1 mediates the binding of eNOS 3'-UTR in eEF1A1. Overexpression of eEF1A1 markedly attenuated the expression of eNOS and luciferase gene fused with eNOS 3'-UTR in both COS-7 cells and bovine aortic endothelial cells (BAECs). Furthermore, adenovirus-mediated overexpression of eEF1A1 increased eNOS mRNA instability, whereas knockdown of eEF1A1 substantially attenuated TNF-alpha-induced destabilization of eNOS mRNA and downregulation of eNOS expression in HUVECs. These results indicate that eEF1A1 is a novel eNOS 3'-UTR binding protein that plays a critical role in mediating TNF-alpha-induced decrease in eNOS mRNA stability.
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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.