Cited by 775Nitric Oxide and Endothelin EffectsAtherosclerosis and Cardiovascular DiseasesAngiogenesis and VEGF in Cancer

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Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life

Yoshizumi, M, Perrella, M A, Burnett, J C, Lee, M E·1993·Circulation Research

DOI 10.1161/01.res.73.1.205

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Abstract

Nitric oxide (NO), which accounts for the biological properties of endothelium-derived relaxing factor, is generated by NO synthase (NOS). The vascular endothelium contains two types of NOS: one is constitutively expressed (cNOS), and the other is inducible. Endothelium-mediated vasorelaxation is impaired in atherosclerotic vessels. To determine whether tumor necrosis factor (TNF)-alpha, which is commonly found in atherosclerotic lesions, has an effect on NOS message, we measured cNOS mRNA levels in TNF-treated human umbilical vein endothelial cells (HUVECs) by RNA blot analysis with a cNOS cDNA probe. TNF-alpha markedly reduced cNOS mRNA levels in HUVECs in a dose- and time-dependent manner. In response to 3 ng/mL TNF-alpha, cNOS mRNA levels began to decrease at 4 hours and diminished to only 5% of control levels at 24 hours. As little as 0.1 ng/mL TNF-alpha reduced cNOS mRNA levels by 50%. This reduction in cNOS message in response to TNF-alpha depended on protein synthesis as it was blocked by cycloheximide. In nuclear runoff experiments, TNF-alpha did not change the rate of cNOS gene transcription. cNOS mRNA is very stable under basal conditions, with a half-life of 48 hours; however, treatment with TNF-alpha shortened this half-life to 3 hours. TNF-alpha thus appears to decrease cNOS mRNA levels by increasing the rate of mRNA degradation. TNF-induced reductions in cNOS mRNA levels may have an important effect on impaired endothelium-mediated vasorelaxation in atherosclerosis.

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Literatur
Deng, M. C.-H. K. (1997) · Steinkopff eBooks · doi:10.1007/978-3-642-48012-6_5
Arginine and the microcirculation
Wijnands, K. A. P. (2015) · Research Publications (Maastricht University) · doi:10.26481/dis.20151127kw
Nitric Oxide
Li, J., & Billiar, T. R. (2002) · Encyclopedia of Molecular Biology · doi:10.1002/047120918x.emb1002
Faculty Opinions recommendation of Endothelial NOS: perspective and recent developments.
Doulias, P. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734261552.793578231
The Interplay of HIV and Long COVID in Sub-Saharan Africa: Mechanisms of Endothelial Dysfunction
Chikopela, T., Mwesigwa, N., Masenga, S. K., Kirabo, A., & Shibao, C. A. (2024) · Current Cardiology Reports · doi:10.1007/s11886-024-02087-6
“Concurrently, it may lead to endothelial dysfunction by inhibiting eNOS expression [52] and reducing NO bioavailability [53].”
Structure-Activity Relationship of Staurosporine Analogs in Regulating Expression of Endothelial Nitric-Oxide Synthase Gene
Li, H., & Förstermann, U. (2000) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)26406-3
Physiology and Pathobiology of Microvascular Endothelium
Pober, J. S. (1984) · Comprehensive physiology · doi:10.1002/j.2040-4603.1984.tb01011.x
Physiology and Pathobiology of the Microvascular Endothelium
Pierce, R. W., & Pober, J. S. (2025) · Physiology in health and disease · doi:10.1007/978-3-031-99609-2_6
Ocena działania antyoksydantów u pacjentów z zaburzeniami erekcji leczonych preparatem hamującym aktywność fosfodiesterazy typu 5
Tomasz, P. (2014)
Genetic vs. Aquired fitness: Metabolic, Vascular and Cardiomyocyte Adaptations
Haram, P. M. (2006) · BIBSYS Brage (BIBSYS (Norway))
FIGURE 3 in A new mid-altitude rainforest species of Typhlops (Serpentes: Typhlopidae) from Madagascar with notes on the taxonomic status of T. boettgeri Boulenger, T. microcephalus Werner, and T. capensis Rendahl
Wallach, V., & Glaw, F. (2009) · INFM-OAR (INFN Catania) · doi:10.5281/zenodo.191504
Nitric Oxide Synthase
Guzman, N. J., & Amoah-Apraku, B. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46806-9_9
“Tumor necrosis decreases the expression of eNOS in human endothelial cells by destabilizing eNOS and shortening its half-life (Yoshizumi et al., 1993).”
Background
Understanding ischemia in children with tuberculous meningitis (iThemba): a protocol paper
Truter, C., Hamilton, M. S., Roux, C. E. L., et al. (2026) · BMC Pediatrics · doi:10.1186/s12887-026-06598-9
“Tumour necrosis factor (TNF)-α induces VEGF production [49] and may cause damage through promotion of thrombosis [50], by reduced cerebral blood flow [51], or reduction in nitric oxide production [52].”
Potentiel des polyphénols à prévenir la dysfonction endothéliale liée au vieillissement et la sénescence des cellules endothéliales
Idris-Khodja, N. (2012) · theses.fr (ABES) · doi:10.70675/b7dd5e95z7adbz45f4zb349z90e37c85791d
Metabolic and cardiovascular effects of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway modulation : Study in the WHHL rabbit as an experimental model of high fructose high fat diet-induced metabolic syndrome.
Moughaizel, M. (2020) · theses.fr (ABES) · doi:10.70675/d21b4f34z8e9az4348za233z7629490bce9e
The association of risk factors, circulatory biomarkers and antihypertensive medications with preeclampsia: a Mendelian randomisation analysis
Wang, S., Meena, D., Huang, J., Otto, G., Savvidou, M. D., & Dehghan, A. (2026) · BMC Medicine · doi:10.21203/rs.3.rs-9202748/v1
Physiology and pathophysiology of hypertension
Fu, Q., Smith, S. A., & Vongpatanasin, W. (2026) · Elsevier eBooks · doi:10.1016/b978-0-12-815389-5.00076-9
Pregnancy Complications and Long-Term Cardiovascular Risk
Minhas, A., Duvall, C., & Hays, A. G. (2026) · Physiology in health and disease · doi:10.1007/978-3-032-26472-5_13
Disfunção endotelial e fator de necrose tumoral-α na malária grave
Neto, S., & dos, L. L. (1993)
Downregulation of eNOS mRNA expression by TNFα: identification and functional characterization of RNA–protein interactions in the 3′UTR
Lai, P. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(03)00296-7 · Cited by 57

Authors: Yoshizumi, M., Perrella, M. A., Burnett, J. C., & Lee, M. E.
Affiliations: Harvard University (US)
ORCID: Yoshizumi, M
Perrella, M A
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1993-07
Volume: 73
Issue: 1
Pages: 205-209
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.73.1.205
OpenAlex: W2145570729
Cited by: 771
References: 0
Citations by year: 2026: 4 · 2025: 5 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 15 · 2020: 16 · 2019: 12 · 2018: 16 · 2017: 14 · 2016: 11 · 2015: 17 · 2014: 35 · 2013: 19 · 2012: 18
FWCI: 21.77
Type: journal article
Language: en
Open access: closed
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: TNF-α, endothelial nitric oxide synthase, constitutive nitric oxide synthase, mRNA stability, mRNA degradation, human umbilical vein endothelial cells, atherosclerosis, cycloheximide, gene transcription
MeSH terms: Amino Acid Oxidoreductases, Base Sequence, Endothelium, Vascular, Half-Life, Humans, Molecular Sequence Data, RNA, Messenger, Transcription, Genetic, Tumor Necrosis Factor-alpha, Umbilical Veins, Down-Regulation, Polymerase Chain Reaction, Nitric Oxide Synthase

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Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life

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