ArticleBiochemistry2008
Nitric oxide regulation of MMP-9 activation and its relationship to modifications of the cysteine switch.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 72 citations in OpenAlex.
- Neuropharmacological effects of calycosin: a translational review of molecular mechanisms and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Protective effects of Aloe vera extract against doxorubicin-induced degeneration in ovarian follicles and stromal cells in mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.PloS one · 2024Article
- Role of Matrix Metalloproteinases in Musculoskeletal Diseases.Biomedicines · 2022Review
- Deciphering the Path ofAntioxidants (Basel, Switzerland) · 2022Article
- Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine-dependent SOD1 monomerization.FEBS open bio · 2022Article
- Thionitrite and Perthionitrite in NO Signaling at Zinc.Angewandte Chemie (International ed. in English) · 2021Article
- Qi-Long-Tian formula extract alleviates symptoms of acute high-altitude diseases via suppressing the inflammation responses in rat.Respiratory research · 2021Article
- A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19.European journal of pharmacology · 2021Review
- S-Nitrosylation: An Emerging Paradigm of Redox Signaling.Antioxidants (Basel, Switzerland) · 2019Review
- Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity.Sports medicine (Auckland, N.Z.) · 2018Review
- The platelet phenotype in patients with ST-segment elevation myocardial infarction is different from non-ST-segment elevation myocardial infarction.Translational research : the journal of laboratory and clinical medicine · 2018Article
- Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.World journal of clinical pediatrics · 2016Review
- Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke.Frontiers in cellular neuroscience · 2016Review
- Hemoglobin-induced nitric oxide synthase overexpression and nitric oxide production contribute to blood-brain barrier disruption in the rat.Journal of molecular neuroscience : MN · 2013Article
- Androgen deprivation by flutamide modulates uPAR, MMP-9 expressions, lipid profile, and oxidative stress: amelioration by daidzein.Molecular and cellular biochemistry · 2013Article
- Article
- Protein S-nitrosylation: role for nitric oxide signaling in neuronal death.Biochimica et biophysica acta · 2012Review
- Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways.Clinical & experimental metastasis · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Matrix metalloproteases (MMPs) are Zn-containing endopeptidases involved in the degradation of extracellular matrix components and are typically secreted in a latent (pro-MMP) form and activated either by proteolytic or oxidative disruption of a conserved cysteine switch. Several recent studies have suggested that nitric oxide (NO) can contribute to the activation of MMPs, but the mechanisms involved are incompletely understood. We investigated the ability of NO to regulate the activation of (pro)MMP-9 using a variety of NO-donor compounds and characterized modifications of the cysteine switch using a synthetic peptide (PRCGVPDLGR) representing the cysteine switch domain of MMP-9. Among the NO-donors used, only S-nitrosocysteine (SNOC) was found to be capable of modest activation of proMMP-9, but S-nitrosoglutathione (GSNO) or the NONOates, DEA-NO, SPER-NO, or DETA-NO, were ineffective. In fact, high concentrations of DETA-NO were found to inhibit MMP-9 activity, presumably by direct interaction with the active-site Zn (2+). Analysis of chemical modifications within the Cys-containing peptide, PRCGVPDLGR, revealed rapid and transient S-nitrosylation by SNOC and GSNO, and formation of mixed disulfides and dimerized peptide as major final products. Similarly, NONOates induced transient S-nitrosylation and primarily peptide dimerization. Coordination of the peptide Cys with a synthetic Zn (2+) complex, to more closely mimic the structure of the active site in proMMP-9, reduced peptide nitrosylation and oxidation by NONOates, but enhanced peptide nitrosylation by SNOC and GSNO. Collectively, our results demonstrate that NO is incapable of directly activating proMMP-9 and that S-nitrosylation of MMP-9 propeptide by NO-donors is unrelated to their ability to regulate MMP-9 activity.
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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.