The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
An S -nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate
Abstract
Red blood cells (RBCs) act as O(2)-responsive transducers of vasodilator and vasoconstrictor activity in lungs and tissues by regulating the availability of nitric oxide (NO). Vasodilation by RBCs is impaired in diseases characterized by hypoxemia. We have proposed that the extent to which RBCs constrict vs. dilate vessels is, at least partly, controlled by a partitioning between NO bound to heme iron and to Cysbeta93 thiol of hemoglobin (Hb). Hemes sequester NO, whereas thiols deploy NO bioactivity. In recent work, we have suggested that specific micropopulations of NO-liganded Hb could support the chemistry of S-nitrosohemoglobin (SNO-Hb) formation. Here, by using nitrite as the source of NO, we demonstrate that a (T state) micropopulation of a heme-NO species, with spectral and chemical properties of Fe(III)NO, acts as a precursor to SNO-Hb formation, accompanying the allosteric transition of Hb to the R state. We also show that at physiological concentrations of nitrite and deoxyHb, a S-nitrosothiol precursor is formed within seconds and produces SNO-Hb in high yield upon its prompt exposure to O(2) or CO. Deoxygenation/reoxygenation cycling of oxyHb in the presence of physiological amounts of nitrite also efficiently produces SNO-Hb. In contrast, high amounts of nitrite or delays in reoxygenation inhibit the production of SNO-Hb. Collectively, our data provide evidence for a physiological S-nitrosothiol synthase activity of tetrameric Hb that depends on NO-Hb micropopulations and suggest that dysfunction of this activity may contribute to the pathophysiology of cardiopulmonary and blood disorders.
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“Several proposed mechanisms have been constructed to explain how nitrite-derived bioactivity can be exported from the red blood cell and these generally involve either a compartment model with submembrane localization of the reaction allowing for inefficient free NO escape, or the formation of another nitrogen oxide such as a nitrosothiol or N2O3 that can get out of the red blood cell and carry NO”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [50]
In the citing paper
“exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro [25, 43, 46-53].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [46]
In the citing paper
“Many reports show that nitrite supplementation to intact organisms is associated with a widespread increase in the concentration of this anion and production of NO-derived species such as S-nitrosothiols or nitrosylhemes in several tissues[25, 43, 46, 48, 49, 96].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [46]
In the citing paper
“A potential mechanism by which nitrite could induce cGMP-independent effects is S-nitrosation of cysteine residues, which is being increasingly recognized as a potential nitrite-induced post-translational modification that can alter protein function[17, 43, 46, 47, 51, 96].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [46]
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Citations
Cites
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
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Kirkwood, B. R., & Sterne, J. A. C. (2014) · Bristol Research (University of Bristol) · Cited by 2,820
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Self-citationBlood Flow Regulation by S -Nitrosohemoglobin in the Physiological Oxygen Gradient
Stamler, J. S., Jia, L., Eu, J. P., McMahon, T. J., Demchenko, I. T., Bonaventura, J., Gernert, K., & Piantadosi, C. A. (1997) · Science · doi:10.1126/science.276.5321.2034 · Cited by 1,050
Self-citationExport by red blood cells of nitric oxide bioactivity
Pawloski, J. R., Hess, D. T., & Stamler, J. S. (2001) · Nature · doi:10.1038/35054560 · Cited by 579
Self-citationReactions between nitric oxide and haemoglobin under physiological conditions
Gow, A. J., & Stamler, J. S. (1998) · Nature · doi:10.1038/34402 · Cited by 562
Self-citationEssential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock
Liu, L., Yan, Y., Zeng, M., Zhang, J., Hanes, M. A., Ahearn, G. S., McMahon, T., Dickfeld, T. L., Marshall, H. E., Que, L. G., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00131-x · Cited by 546
Self-citationEnzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Huang, Z. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24650 · Cited by 520
Singel, D. J., & Stamler, J. S. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.67.060603.090918 · Cited by 481
Self-citationNitric oxide in the human respiratory cycle
McMahon, T., Moon, R. E., Luschinger, B. P., Carraway, M. S., Stone, A. E., Stolp, B. W., Gow, A. J., Pawloski, J. R., Watke, P., Singel, D. J., et al. (2002) · Nature Medicine · doi:10.1038/nm718 · Cited by 462
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Research works printed but not linked: 1
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Evolution of adverse changes in stored RBCs
Bennett‐Guerrero, E., Veldman, T. H., Doctor, A., Telen, M. J., Ortel, T. L., Reid, T. S., Mulherin, M. A., Zhu, H., Buck, R. D., Califf, R. M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708160104 · Cited by 614
Shiva, S., Huang, Z., Grubina, R., Sun, J., Ringwood, L. A., MacArthur, P. H., Xu, X., Murphy, E., Darley-Usmar, V. M., & Gladwin, M. T. (2007) · Circulation Research · doi:10.1161/01.res.0000260171.52224.6b · Cited by 599
Nitrite as Regulator of Hypoxic Signaling in Mammalian Physiology
van Faassen, E. E., Bahrami, S., Feelisch, M., Hogg, N., Kelm, M., Kim‐Shapiro, D. B., Kozlov, A. V., Li, H., Lundberg, J. O., Mason, R., et al. (2009) · Medicinal Research Reviews · doi:10.1002/med.20151 · Cited by 435
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Ingested nitrate and nitrite and stomach cancer risk: An updated review
Bryan, N. S., Alexander, D. D., Coughlin, J. R., Milkowski, A. L., & Boffetta, P. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.07.062 · Cited by 335
Metadata
- Authors
- Angelo, M., Singel, D. J., & Stamler, J. S.
- Affiliations
- Duke Medical Center (US)
- Montana State University (US)
- Duke University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-05-30
- Volume
- 103
- Issue
- 22
- Pages
- 8366-8371
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1989100763
- Cited by
- 233
- References
- 38
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 4 · 2015: 5 · 2014: 9 · 2013: 10 · 2012: 19
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Heart, Lung, and Blood Institute (P01HL042444, R01 HL42444)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- hemoglobin, S-nitrosohemoglobin, nitrite, nitric oxide, T state, allosteric transition, R state, erythrocytes, vasodilation, hypoxemia
- MeSH terms
- Hemoglobins, Humans, Iron, Nitrites, Oxygen, Spectrum Analysis, Substrate Specificity, S-Nitrosothiols
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