The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Transcriptional and Posttranscriptional Regulation of Endothelial Nitric Oxide Synthase Expression by Hydrogen Peroxide
Abstract
Abstract —Diverse stimuli, including shear stress, cyclic strain, oxidized LDL, hyperglycemia, and cell growth, modulate endothelial nitric oxide synthase (eNOS) expression. Although seemingly unrelated, these may all alter cellular redox state, suggesting that reactive oxygen intermediates might modulate eNOS expression. The present study was designed to test this hypothesis. Exposure of bovine aortic endothelial cells for 24 hours to paraquat, a superoxide (O 2 −· )–generating compound, did not affect eNOS mRNA levels. However, cotreatment with paraquat and either Cu 2+ /Zn 2+ superoxide dismutase or the superoxide dismutase mimetic tetrakis(4-benzoic acid)porphyrin chloride increased eNOS mRNA by 2.3- and 2.2-fold, respectively, implicating a role for H 2 O 2 . Direct addition of 100 and 150 μmol/L H 2 O 2 caused increases in bovine aortic endothelial cell eNOS mRNA that were dependent on concentration (ie, 3.1- and 5.2-fold increases) and time, and elevated eNOS protein expression and enzyme activity, accordingly. Nuclear run-on and 5,6-dichloro-1-β- d -ribofuranosylbenzimidazole–chase studies showed that H 2 O 2 caused a 3.0-fold increase in eNOS gene transcription and a 2.8-fold increase in eNOS mRNA half-life. Induction of eNOS by H 2 O 2 was not affected by the hydroxyl radical scavenger DMSO, mannitol, or N-tert-butyl -α-phenylnitrone, but it was inhibited by the antioxidants N -acetylcysteine, ebselen, and exogenously added catalase. Unlike H 2 O 2 , the 4.0-fold induction of eNOS by shear stress (15 dyne/cm 2 for 6 hours) was not inhibited by N -acetylcysteine or exogenous catalase. In conclusion, H 2 O 2 increases eNOS expression through transcriptional and post-transcriptional mechanisms. Although H 2 O 2 does not mediate shear-dependent eNOS regulation, it is likely to be involved in regulation of eNOS expression in response to other physiological and/or pathophysiological stimuli.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The signaling mechanisms of hydrogen peroxide in ECs (941) lead to the increased activity of eNOS and other enzymes (121, 141, 193, 251, 815, 940).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [251]
Citations
Cites
Upregulation of Endothelial Nitric Oxide Synthase by HMG CoA Reductase Inhibitors
Laufs, U., Fata, V. L., Plutzky, J., & Liao, J. K. (1998) · Circulation · doi:10.1161/01.cir.97.12.1129 · Cited by 1,837
The Dynamic Response of Vascular Endothelial Cells to Fluid Shear Stress
Dewey, C. F., Bussolari, S. R., Gimbrone, M. A., & Davies, P. F. (1981) · Journal of Biomechanical Engineering · doi:10.1115/1.3138276 · Cited by 1,137
Yoshizumi, M., Perrella, M. A., Burnett, J. C., & Lee, M. E. (1993) · Circulation Research · doi:10.1161/01.res.73.1.205 · Cited by 771
Cosentino, F., Hishikawa, K., Katušić, Z. S., & Lüscher, T. F. (1997) · Circulation · doi:10.1161/01.cir.96.1.25 · Cited by 762
Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III)
Förstermann, U., Boissel, J., & Kleinert, H. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.10.773 · Cited by 647
Oscillatory and Steady Laminar Shear Stress Differentially Affect Human Endothelial Redox State
Keulenaer, G. W. D., Chappell, D. C., Ishizaka, N., Nerem, R. M., Alexander, R. W., & Griendling, K. K. (1998) · Circulation Research · doi:10.1161/01.res.82.10.1094 · Cited by 605
Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells.
Awolesi, M. A., Sessa, W. C., & Sumpio, B. E. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118181 · Cited by 328
Bouloumié, A., Bauersachs, J. K., Linz, W., Schölkens, B. A., Wiemer, G., Fleming, I., & Busse, R. (1997) · Hypertension · doi:10.1161/01.hyp.30.4.934 · Cited by 303
Shear Stress Modulates Expression of Cu/Zn Superoxide Dismutase in Human Aortic Endothelial Cells
Inoue, N., Ramasamy, S., Fukai, T., Nerem, R. M., & Harrison, D. G. (1996) · Circulation Research · doi:10.1161/01.res.79.1.32 · Cited by 299
Self-citationReactive Oxygen Species and Antioxidants in Signal Transduction and Gene Expression
Palmer, H. J., & Paulson, K. E. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1997.tb01561.x · Cited by 277
Flagged first, then by citations
Research works printed but not linked: 14
- 10.1161/hyp.31.2.582 · DOI
- 10.1161/atvb.15.8.1255 · DOI
- 10.1161/hyp.32.2.351 · DOI
- 10.1161/res.85.7.588 · DOI
- 10.1161/circ.97.12.1129 · DOI
- 10.1161/res.74.4.7511072 · DOI
- 10.1161/circ.96.1.25 · DOI
- 10.1161/res.82.10.1094 · DOI
- 10.1161/res.81.1.1 · DOI
- 10.1161/atvb.17.12.3570 · DOI
- 10.1161/hyp.31.1.125 · DOI
- 10.1161/res.73.1.7685252 · DOI
- 10.1161/res.79.1.32 · DOI
- 10.1161/hyp.30.4.934 · DOI
Cited by
Sorted by citations
Items 401–429 of 429
Reactive Oxygen Species (ROS) and the Sensory Neurovascular Component
Graepel, R., Bodkin, J. V., & Brain, S. D. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-600-9_4
Salisbury, D. L. (2014) · University of Minnesota Digital Conservancy (University of Minnesota)
Mthethwa, M. (2015) · SUNScholar (Stellenbosch University)
Medizin, I., & Böhm, M. (2005)
The effects of smoking on endothelial cell function
Barua, R. S. (2002) · Surrey Research Insight Open Access (The University of Surrey)
Free Radicals as Atherosclerotic Risk in Relation to Nitric Oxide
Hayashi, T., & Iguchi, A. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-373866-0.00021-6
Trane, A. (2016) · cIRcle (University of British Columbia) · doi:10.14288/1.0307160
Oxygen radical generation by lymphoblast NADPH oxidase in hypertension
Pettit, A. I. (2006) · Leicester Research Archive (University of Leicester)
Levy, A. (2011) · UWSpace (University of Waterloo)
The Effect of Cardiovascular Risk Factors on the Coronary Circulation
Valenzuela-García, L. F., Matsuzawa, Y., & Lerman, A. (2017) · Springer eBooks · doi:10.1007/978-1-4471-5245-3_6
Mélançon, S. (2005) · Corpus Université Laval (Université Laval)
Mediators in cardiovascular disease: association with Raynaud’s phenomenon
Abdulle, A. E. (2021) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.194678419
Kojda, G. (2001) · Steinkopff eBooks · doi:10.1007/978-3-642-87803-9_1
Denniss, S. G. (2011) · UWSpace (University of Waterloo)
Mechanismen potenziell vasoprotektiver Wirkungen von NO
Kojda, G. (2001) · Steinkopff eBooks · doi:10.1007/978-3-642-87803-9_3
Kang, S. U., Kim, H. J., Ma, S., Oh, D.-Y., Jang, J. Y., Seo, C., Lee, Y. S., & Kim, C.-H. (2024) · Figshare · doi:10.6084/m9.figshare.25248838
Junglas, T., Daiber, A., Kuntić, I., Valar, A., Zheng, J., Oelze, M. W., Strohm, L., Ubbens, H., Hahad, O., Jiménez, M. T. B., et al. (2026) · Antioxidants · doi:10.3390/antiox15010106
Idris-Khodja, N. (2012) · theses.fr (ABES) · doi:10.70675/b7dd5e95z7adbz45f4zb349z90e37c85791d
Echeverría‐Rodríguez, O., Rodríguez, S. R., Torres, S. D. H., Riveros‐Rosas, H., Ortiz, I. A. G., Molina, R. V., & Vilchis‐Landeros, M. M. (2026) · Vascular Pharmacology · doi:10.1016/j.vph.2026.107692
The role of zinc and reactive oxygen species in the regulation of endothelial nitric oxide synthase
Wilham, J. M. (2007) · The Mathematics Enthusiast
Yogaratnam, J. Z. (2011) · Repository@Hull (Worktribe) (University of Hull)
Der NO/cGMP-Signaltransduktionsweg
Kojda, G. (2001) · Steinkopff eBooks · doi:10.1007/978-3-642-87803-9_2
Biodisponibilidade cardiovascular do oxdo nitrico em camundongos LDLr-/-
Wanschel, A. C. B. A. (2010) · doi:10.47749/t/unicamp.2010.480714
Metadata
- Authors
- Drummond, G. R., Cai, H., Davis, M. E., Ramasamy, S., & Harrison, D. G.
- Affiliations
- Emory University (US)
- Venue
- Circulation Research
- Published
- 2000-02-18
- Volume
- 86
- Issue
- 3
- Pages
- 347-354
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2110361956
- Cited by
- 430
- References
- 34
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 13 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 14 · 2016: 13 · 2015: 15 · 2014: 19 · 2013: 15 · 2012: 16
- FWCI
- 16.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health (5r01hl059248-04)
- National Heart, Lung, and Blood Institute (HL 58000, HL 59248, HL 39000 6, P01HL058000)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- endothelial nitric oxide synthase, hydrogen peroxide, mRNA stability, post-transcriptional regulation, shear stress, superoxide dismutase, paraquat, redox state, reactive oxygen species, antioxidant inhibition, N-acetylcysteine, ebselen, catalase, endothelial cells, oxidative stress, nitric oxide signaling
- MeSH terms
- Animals, Cattle, Cells, Cultured, Enzyme Induction, Humans, Hydrogen Peroxide, Paraquat, Protein Processing, Post-Translational, RNA, Messenger, Stress, Mechanical, Time Factors, Transcription, Genetic, Free Radical Scavengers, Oxidants, Nitric Oxide Synthase, RNA Stability, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
