S -Nitrosylation in Cardiovascular Signaling
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Abstract : Well over 2 decades have passed since the endothelium-derived relaxation factor was reported to be the gaseous molecule nitric oxide (NO). Although soluble guanylyl cyclase (which generates cyclic guanosine monophosphate, cGMP) was the first identified receptor for NO, it has become increasingly clear that NO exerts a ubiquitous influence in a cGMP-independent manner. In particular, many, if not most, effects of NO are mediated by S -nitrosylation, the covalent modification of a protein cysteine thiol by an NO group to generate an S -nitrosothiol (SNO). Moreover, within the current framework of NO biology, endothelium-derived relaxation factor activity (ie, G protein–coupled receptor–mediated, or shear-induced endothelium-derived NO bioactivity) is understood to involve a central role for SNOs, acting both as second messengers and signal effectors. Furthermore, essential roles for S -nitrosylation have been implicated in virtually all major functions of NO in the cardiovascular system. Here, we review the basic biochemistry of S -nitrosylation (and denitrosylation), discuss the role of S -nitrosylation in the vascular and cardiac functions of NO, and identify current and potential clinical applications.
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Global kinetic analysis suggests that the main source of NO2· in vivo may be the decomposition of peroxynitrite.
“Global kinetic analysis of the reactions involved suggests that the main source of NO2· in vivo may be the decomposition of peroxynitrite (585).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [585]
NO regulates the activities of enzymes and signaling proteins by S-nitrosylation of thiol moieties.
“Furthermore, NO regulates the activities of enzymes and signaling proteins by S-nitrosylation of thiol moieties (2).”
From Dietary nitrate, nitric oxide, and restenosis (2011) · cites this paper as [2]
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Nitric oxide regulates endocytosis by S -nitrosylation of dynamin
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Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation
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Hypoxic Vasodilation by Red Blood Cells
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Regulation of platelet granule exocytosis by S-nitrosylation
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S-Nitrosylation of Cardiac Ion Channels
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Self-citationHuman Carbonyl Reductase 1 Is an S-Nitrosoglutathione Reductase
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Estrogen Receptor-β Activation Results in S-Nitrosylation of Proteins Involved in Cardioprotection
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Calcium Regulates S-Nitrosylation, Denitrosylation, and Activity of Tissue Transglutaminase
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Reduced Nitric Oxide Causes Age-Associated Impairment of Circadian Rhythmicity
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Autoregulation of blood flow by oxygen lack
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Self-citationRed Blood Cell Nitric Oxide as an Endocrine Vasoregulator
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Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism
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Shear flow increases S-nitrosylation of proteins in endothelial cells
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TNFα and oxLDL Reduce Protein S-Nitrosylation in Endothelial Cells
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A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases
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Nitric Oxide–Mediated Zinc Release Contributes to Hypoxic Regulation of Pulmonary Vascular Tone
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Redox- and Calmodulin-dependent S-Nitrosylation of the KCNQ1 Channel
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Kinetic and Cellular Characterization of Novel Inhibitors of S-Nitrosoglutathione Reductase
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S-Nitrosation Controls Gating and Conductance of the α1 Subunit of Class C L-type Ca2+ Channels
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Self-citationModulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin
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The Science of Stroke: Mechanisms in Search of Treatments
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Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis
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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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Ingested nitrate and nitrite and stomach cancer risk: An updated review
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- Authors
- Lima, B., Forrester, M. T., Hess, D. T., & Stamler, J. S.
- Affiliations
- Duke University (US)
- Corresponding author
- Stamler, Jonathan S.
- Venue
- Circulation Research
- Published
- 2010-03-05
- Volume
- 106
- Issue
- 4
- Pages
- 633-646
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC2891248
- OpenAlex
- W2143004446
- Cited by
- 490
- References
- 175
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 16 · 2023: 16 · 2022: 22 · 2021: 28 · 2020: 24 · 2019: 22 · 2018: 31 · 2017: 27 · 2016: 35 · 2015: 39 · 2014: 44 · 2013: 39 · 2012: 48
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HL-075443)
- National Heart, Lung, and Blood Institute (R01HL095463, R01HL091876, R01HL059130, P01HL075443, R01HL096673)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- S-nitrosylation, nitric oxide, S-nitrosothiols, denitrosylation, cGMP-independent signaling, G protein-coupled receptors, cardiovascular signaling, vascular function, cardiac function, second messengers, clinical application
- MeSH terms
- Animals, Cardiovascular Diseases, Cardiovascular System, Endothelium, Vascular, Cyclic GMP, Humans, Inflammation, Myocardium, Nitric Oxide, Protein Processing, Post-Translational, Vascular Resistance, Signal Transduction, Apoptosis, Neovascularization, Physiologic, S-Nitrosothiols, Endothelium-Dependent Relaxing Factors
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