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Cited by 186Nitric Oxide and Endothelin EffectsNF-κB Signaling PathwaysCell Adhesion Molecules Research

The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.

Tumor Necrosis Factor-α Inhibits Endothelial Nitric-oxide Synthase Gene Promoter Activity in Bovine Aortic Endothelial Cells

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Anderson, Hope D.I., Rahmutula, Dolkun, Gardner, David G.·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m309552200
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Abstract

Tumor necrosis factor-alpha (TNF-alpha) has been shown to reduce endothelial nitric-oxide synthase (eNOS) gene expression through post-transcriptional regulation of mRNA stability. The current study documented an independent effect of the cytokine on the eNOS gene promoter. TNF-alpha effected a time- and dose-dependent reduction in activity of a transiently transfected human -1197 eNOS-luciferase reporter. This reduction was inhibited by co-transfection of dominant negative IKKbeta as well as a nonphosphorylatable constitutively suppressive mutant of IkappaB implying involvement of the NFkappaB cascade in the inhibitory effect. The locus of the TNF-alpha-dependent inhibition was traced to two Sp1-binding sites positioned between -109 and -95 and -81 and -67 relative to the transcription start site. Electrophoretic mobility shift analysis and immunoperturbation studies showed evidence for Sp1 and Sp3 binding to each element. TNF-alpha treatment had no effect on the binding pattern to the downstream (-81 to -67) site but did suppress association of Sp1 and Sp3 to the upstream (-109 to -95) site. Collectively, these data indicate that TNF-alpha exerts transcriptional, as well as post-transcriptional, effects on eNOS gene expression and suggest a potential mechanism to account for the endothelial dysfunction that accompanies disorders such as diabetes mellitus and heart failure.

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Citations

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Research works printed but not linked: 7

  1. Furchgott, 1987, Blood Vessels., 24, 145
  2. Channon, 2002, J. Physiol. Pharmacol., 53, 515
  3. Meininger, 2000, Biochem. J., 349, 353, 10.1042/bj3490353 · DOI
  4. Ding, 2000, Am. J. Physiol., 279, E11
  5. Tickerhoof, 2003, Am. J. Physiol., 285, H2694
  6. Johnson, 1994, Am. J. Physiol., 267, L318
  7. Zhang, 1997, Res. Commun. Mol. Pathol. Pharmacol., 96, 71

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Metadata

Authors
Anderson, H. D. I., Rahmutula, D., & Gardner, D. G.
Affiliations
University of California, San Francisco (US)
Corresponding author
Gardner, David G.
ORCID
Anderson, Hope D.I.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-01
Volume
279
Issue
2
Pages
963-969
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m309552200
OpenAlex
W1984870795
Cited by
186
References
69
Citations by year
2026: 6 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 11 · 2015: 2 · 2014: 10 · 2013: 8 · 2012: 10
FWCI
8.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL-45637, R01HL045637)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK-63720, P30DK063720)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
TNF-α, endothelial nitric oxide synthase, transcriptional regulation, Sp1 binding site, Sp3, NF-κB signaling, IκB, IKKβ, endothelial dysfunction, bovine aortic endothelial cells, luciferase reporter
MeSH terms
NF-KappaB Inhibitor alpha, Animals, Aorta, Cattle, Cell Nucleus, DNA-Binding Proteins, Dose-Response Relationship, Drug, Endothelium, Vascular, Genes, Dominant, Humans, Luciferases, Mutation, Phosphorylation, Plasmids, Promoter Regions, Genetic, Protein Binding, RNA Processing, Post-Transcriptional, RNA, Messenger, Time Factors, Transcription Factors, Transfection, Tumor Necrosis Factor-alpha, Blotting, Western, Sp1 Transcription Factor, Protein Serine-Threonine Kinases, Genes, Reporter, Nitric Oxide Synthase, I-kappa B Proteins, Endothelial Cells, I-kappa B Kinase, Sp3 Transcription Factor, Nitric Oxide Synthase Type III

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