The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite
Open accessAbstract
Nitric oxide (NO) is produced by NO synthase (NOS) in many cells and plays important roles in the neuronal, muscular, cardiovascular, and immune systems.In various disease conditions, all three types of NOS (neuronal, inducible, and endothelial) are reported to generate oxidants through unknown mechanisms.We present here the first evidence that peroxynitrite (ONOO -) releases zinc from the zinc-thiolate cluster of endothelial NOS (eNOS) and presumably forms disulfide bonds between the monomers.As a result, disruption of the otherwise SDS-resistant eNOS dimers occurs under reducing conditions.eNOS catalytic activity is exquisitely sensitive to ONOO -, which decreases NO synthesis and increases superoxide anion (O 2 .-)production by the enzyme.The reducing cofactor tetrahydrobiopterin is not oxidized, nor does it prevent oxidation of eNOS by the same low concentrations of OONO -.Furthermore, eNOS derived from endothelial cells exposed to elevated glucose produces more O 2 .-,and, like eNOS purified from diabetic LDL receptor-deficient mice, contains less zinc and fewer SDS-resistant dimers.Hence, eNOS exposure to oxidants including ONOO -causes increased enzymatic uncoupling and generation of O 2 .-indiabetes, contributing further to endothelial cell oxidant stress.Regulation of the zinc-thiolate center of NOS by ONOO -provides a novel mechanism for modulation of the enzyme function in disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Mitochondrial hydrogen peroxide can oxidize the catalytic subunit of AMP kinase, leading to its autophosphorylation and subsequent activation to modulate metabolism within the cell (481, 1067).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1067]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Regulation of biosynthesis of nitric oxide.
Nathan, C., & Xie, Q. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36703-0 · Cited by 1,669
Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors
Vásquez-Vivar, J., Kalyanaraman, B., Martásek, P., Hogg, N., Masters, B. S. S., Karoui, H., Tordo, P., & Pritchard, K. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9220 · Cited by 1,484
Nitric oxide synthase structure and mechanism
Marletta, M. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31375-9 · Cited by 1,338
Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus
Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M. P., Thaiss, F., Stahl, R. A. K., Warnholtz, A., et al. (2001) · Circulation Research · doi:10.1161/01.res.88.2.e14 · Cited by 1,191
Nitric oxide synthases: which, where, how, and why?
Michel, T. M., & Féron, O. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119750 · Cited by 1,024
Oxidative Damage and Tyrosine Nitration from Peroxynitrite
Beckman, J. S. (1996) · Chemical Research in Toxicology · doi:10.1021/tx9501445 · Cited by 993
Pollock, J. S., Förstermann, U., Mitchell, J. A., Warner, T. D., Schmidt, H. H. H. W., Nakane, M., & Murad, F. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10480 · Cited by 979
Activation of molecular oxygen by flavins and flavoproteins.
Massey, V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31664-2 · Cited by 823
Cosentino, F., Hishikawa, K., Katušić, Z. S., & Lüscher, T. F. (1997) · Circulation · doi:10.1161/01.cir.96.1.25 · Cited by 762
Research works printed but not linked: 1
- Katusic, 2001, Am J Physiol, 281, H981
Cited by
Sorted by citations
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace
Förstermann, U., & Münzel, T. (2006) · Circulation · doi:10.1161/circulationaha.105.602532 · Cited by 1,957
Mészáros, B., Erdős, G., & Dosztányi, Z. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky384 · Cited by 1,454
Metadata
- Authors
- Zou, M.-H., Shi, C., & Cohen, R. A.
- Affiliations
- Boston University (US)
- Corresponding author
- Zou, Ming-Hui
- Venue
- Journal of Clinical Investigation
- Published
- 2002-03-15
- Volume
- 109
- Issue
- 6
- Pages
- 817-826
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4254181710
- Cited by
- 494
- References
- 48
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 19 · 2021: 12 · 2020: 17 · 2019: 15 · 2018: 19 · 2017: 23 · 2016: 15 · 2015: 22 · 2014: 22 · 2013: 22 · 2012: 29
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (PO1 HL)
- 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
- peroxynitrite, endothelial nitric oxide synthase, superoxide production, tetrahydrobiopterin, disulfide bonds, oxidative stress, diabetes mellitus, endothelial cells, nitric oxide production
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
