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S-Nitrosohemoglobin Is Unstable in the Reductive Erythrocyte Environment and Lacks O2/NO-linked Allosteric Function
Open accessAbstract
Our previous results run counter to the hypothesis that S-nitrosohemoglobin (SNO-Hb) serves as an in vivo reservoir for NO from which NO release is allosterically linked to oxygen release. We show here that SNO-Hb undergoes reductive decomposition in erythrocytes, whereas it is stable in purified solutions and in erythrocyte lysates treated with an oxidant such as ferricyanide. Using an extensively validated methodology that eliminates background nitrite and stabilizes erythrocyte S-nitrosothiols, we find the levels of SNO-Hb in the basal human circulation, including red cell membrane fractions, were 46 +/- 17 nm in human arterial erythrocytes and 69 +/- 11 nm in venous erythrocytes, incompatible with the postulated reservoir function of SNO-Hb. Moreover, we performed experiments on human red blood cells in which we elevated the levels of SNO-Hb to 10,000 times the normal in vivo levels. The elevated levels of intra-erythrocytic SNO-Hb fell rapidly, independent of oxygen tension and hemoglobin saturation. Most of the NO released during this process was oxidized to nitrate. A fraction (25%) was exported as S-nitrosothiol, but this fraction was not increased at low oxygen tensions that favor the deoxy (T-state) conformation of Hb. Results of these studies show that, within the redox-active erythrocyte environment, the beta-globin cysteine 93 is maintained in a reduced state, necessary for normal oxygen affinity, and incapable of oxygen-linked NO storage and delivery.
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“However studies conducted in this area over the last few years have unraveled mechanisms by which NO bioactivity in blood and in tissue have been preserved in the form of nitrite, nitrate, S-nitrosothiols (RSNO), N-nitrosamines (RNNO), nitrosylhemoglobin (NOHb), and S-nitrosohemoglobin (SNOHb) [16–21].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [18]
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Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Oxidized Redox State of Glutathione in the Endoplasmic Reticulum
Hwang, C., Sinskey, A. J., & Lodish, H. F. (1992) · Science · doi:10.1126/science.1523409 · Cited by 1,968
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-citationNitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.
Stamler, J. S., Jaraki, O., Osborne, J., Simon, D. I., Keaney, J., Vita, J., Singel, D., Valeri, C. R., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7674 · Cited by 1,238
Activation of the OxyR Transcription Factor by Reversible Disulfide Bond Formation
Zheng, M., Åslund, F., & Storz, G. (1998) · Science · doi:10.1126/science.279.5357.1718 · Cited by 1,197
Blood 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
Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways.
Gaston, B. M., Reilly, J., Drazen, J. M., Fackler, J. C., Ramdev, P., Arnelle, D. R., Mullins, M. E., Sugarbaker, D. J., Chee, C., Singel, D. J., et al. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10957 · Cited by 620
Export 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
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Research works printed but not linked: 1
- Garel, 1984, Mol. Pharmacol., 26, 559
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Items 101–159 of 159
Jacobsen, S. B., Hansen, M. N., Jensen, F. B., Skovgaard, N., Wang, T., & Fago, A. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.070367 · Cited by 26
Nitric Oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish,Squalus acanthias
Swenson, K. E., Eveland, R. L., Gladwin, M. T., & Swenson, K. E. (2005) · Journal of Experimental Zoology Part A Comparative Experimental Biology · doi:10.1002/jez.a.145 · Cited by 26
Self-citationRoutes for Formation of S-Nitrosothiols in Blood
Nagababu, E., & Rifkind, J. M. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9321-2 · Cited by 25
Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin
Deem, S. A., Kim, S. S., Min, J.-H., Eveland, R. L., Moulding, J., Martyr, S. E., Wang, X., Swenson, E. R., & Gladwin, M. T. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00310.2004 · Cited by 24
Self-citationLi, J., LoBue, A., Heuser, S. K., & Cortese-Krott, M. M. (2024) · Antioxidants · doi:10.3390/antiox13020179 · Cited by 25
Recent insights into nitrite signaling processes in blood
Helms, C. C., Liu, X., & Kim‐Shapiro, D. B. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0263 · Cited by 23
Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins
Bonaventura, C., Henkens, R. W., Alayash, A. I., & Crumbliss, A. L. (2007) · IUBMB Life · doi:10.1080/15216540601188546 · Cited by 23
Self-citationArtery-to-vein differences in nitric oxide metabolites are diminished in sepsis*
Morgan, M. A. M., Frasier, L. M., Stewart, J. C., Mack, C. M., Gough, M. S., Graves, B. T., Apostolakos, M. J., Doolin, K. P., Darling, D. C., Frampton, M. W., et al. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181d16a3e · Cited by 22
DHAWAN, V. M., Schwalb, D. J., Shumway, M. J., Warren, M. C., Wexler, R. S., Zemtseva, I. S., Zifcak, B. M., & Janero, D. R. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.06.011 · Cited by 22
NO metabolite flux across the human coronary circulation
Rogers, S. C., Khalatbari, A., Datta, B. N., Ellery, S. M., PAUL, V., Frenneaux, M. P., & JAMES, P. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.04.019 · Cited by 22
Alayash, A. I. (2004) · Antioxidants and Redox Signaling · doi:10.1089/ars.2004.6.941 · Cited by 21
Nitric oxide scavenging by hemoglobin regulates hypoxic pulmonary vasoconstriction
Deem, S. A. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.11.025 · Cited by 21
Rassaf, T., Kleinbongard, P., & Kelm, M. (2005) · Kidney & Blood Pressure Research · doi:10.1159/000090188 · Cited by 21
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Doctor, A., & Gaston, B. M. (2006) · Blood · doi:10.1182/blood-2006-05-026047 · Cited by 20
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Fago, A., Crumbliss, A. L., Hendrich, M. P., Pearce, L. L., Peterson, J., Henkens, R. W., & Bonaventura, C. (2013) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2013.04.017 · Cited by 20
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Saldanha, C., Almeida, J. P., & Silva-Herdade, A. S. (2014) · Biosensors · doi:10.3390/bios4010001 · Cited by 18
Herold, S. (2003) · Comptes Rendus Biologies · doi:10.1016/s1631-0691(03)00149-5 · Cited by 18
Yi, J., Khan, M. A., Lee, J., & Richter-Addo, G. B. (2005) · Nitric Oxide · doi:10.1016/j.niox.2005.03.005 · Cited by 18
Basu, S., Ricart, K. C., Gladwin, M. T., Patel, R. P., & Kim‐Shapiro, D. B. (2022) · Nitric Oxide · doi:10.1016/j.niox.2022.01.006 · Cited by 18
Self-citationBailey, D. M., Bain, A. R., Hoiland, R. L., Barak, O. F., Drviš, I., Stacey, B. S., Iannetelli, A., Davison, G. W., Dahl, R. H., Berg, R. M. G., et al. (2024) · The Journal of Physiology · doi:10.1113/jp285555 · Cited by 17
Inhaled Nitric Oxide and Neuroprotection in Preterm Infants
Marks, J. D., & Schreiber, M. D. (2008) · Clinics in Perinatology · doi:10.1016/j.clp.2008.07.015 · Cited by 17
Pegylated hemoglobins mechanisms to avoid vasoconstriction and maintain perfusion
Cabrales, P., & Friedman, J. M. (2007) · Transfusion Alternatives in Transfusion Medicine · doi:10.1111/j.1778-428x.2007.00090.x · Cited by 17
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Katona, M., Gladwin, M. T., & Straub, A. C. (2023) · Annual Review of Physiology · doi:10.1146/annurev-physiol-031522-021457 · Cited by 17
Self-citationHwang, S., Cha, W., & Meyerhoff, M. E. (2007) · Electroanalysis · doi:10.1002/elan.200704053 · Cited by 16
Pathobiology of the Human Erythrocyte and Its Hemoglobins
Steinberg, M. H., Benz, E. J. J., Adewoye, A. H., & Ebert, B. L. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35762-3.00033-0 · Cited by 15
Kumar, N., Astegno, A., Chen, J., Giorgetti, A., & Dominici, P. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050640 · Cited by 14
Fritsch, T., Brouzos, P., Heinrich, K., Kelm, M., Rassaf, T., Hering, P., Kleinbongard, P., & Mürtz, M. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.03.002 · Cited by 14
Critical Redox and Allosteric Aspects of Nitric Oxide Interactions with Hemoglobin
Bonaventura, C., Fago, A., Henkens, R. W., & Crumbliss, A. L. (2004) · Antioxidants and Redox Signaling · doi:10.1089/ars.2004.6.979 · Cited by 14
Self-citationDybaś, J., Berkowicz, P., Proniewski, B., Dziedzic-Kocurek, K., Stanek, J. J., Barańśka, M., Chłopicki, S., & Marzec, K. M. (2018) · The Analyst · doi:10.1039/c8an00302e · Cited by 13
Reductive nitrosylation and S-nitrosation of hemoglobin in inhomogeneous nitric oxide solutions
Han, T. H., Fukuto, J. M., & Liao, J. C. (2004) · Nitric Oxide · doi:10.1016/j.niox.2004.03.003 · Cited by 11
Nitric Oxide Metabolism in Adults With Cyanotic Congenital Heart Disease
Han, T. H., Perloff, J. K., & Liao, J. C. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.10.024 · Cited by 10
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Patel, R. P., Yuan, S. S., & Kevil, C. G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804273-1.00004-1 · Cited by 9
Tao, W., Yerbulekova, A., Moore, C. E., Shafaat, H. S., & Zhang, S. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.1c12799 · Cited by 9
Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites
Liu, T., Zhang, M., Duot, A., Mukosera, G. T., Schroeder, H. J., Power, G. G., & Blood, A. B. (2023) · Antioxidants · doi:10.3390/antiox12091672 · Cited by 6
Fenza, R. D., Yu, B., Carroll, R. W., & Berra, L. M. (2022) · Journal of Visualized Experiments · doi:10.3791/63107 · Cited by 8
Nitrate, nitrite and nitric oxide in gastric mucosal defense.
Petersson, J. H. (2008) · Uppsala University Publications (Uppsala University) · Cited by 6
The role of blood nitrite in the control of hypoxic vasodilation
Fago, A., & Jensen, F. B. (2007) · Advances in experimental biology · doi:10.1016/s1872-2423(07)01009-5 · Cited by 5
Heme Protein Metabolism of NO and Nitrite
Kim‐Shapiro, D. B., & Gladwin, M. T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804273-1.00006-5 · Cited by 5
Self-citationS-nitrosated proteins: formation, metabolism, and function
Yang, Y. A., & Loscalzo, J. (2007) · Elsevier eBooks · doi:10.1016/b978-044452236-8/50010-1 · Cited by 5
Winyard, P. G., Knight, I., Shaw, F. L., Rocks, S. A., Davies, C. A., Eggleton, P., Haigh, R. C., Whiteman, M., & Benjamin, N. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)01208-1 · Cited by 4
Nitrite and nitrosospecies in blood and tissue: approaching the gap between bench and bedside
Rassaf, T., & Kelm, M. (2007) · Elsevier eBooks · doi:10.1016/b978-044452236-8/50013-7 · Cited by 4
Effect of storage levels of nitric oxide derivatives in blood components
Qazi, M. A., Rizzatti, F. G., Piknova, B., Sibmooh, N., Stroncek, D. F., & Schechter, A. N. (2012) · F1000Research · doi:10.12688/f1000research.1-35.v1 · Cited by 4
Self-citationAscenzi, P., Petrella, G., & Coletta, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.05.196 · Cited by 3
Saldanha, C., & Silva-Herdade, A. S. (2018) · InTech eBooks · doi:10.5772/intechopen.75931 · Cited by 1
Glebov, A., & Зинчук, В. В. (2005) · PubMed · Cited by 1
Kim‐Shapiro, D. B., Gladwin, M. T., Patel, R. P., & Hogg, N. (2008) · Elsevier eBooks · doi:10.1016/b978-044452839-1.50012-7 · Cited by 1
Self-citationNitric Oxide Generating Polymers (NOGPs).
Hwang, S. (2007) · Deep Blue (University of Michigan)
S-nitrosothiols in Cell Signaling
Loscalzo, J. (2003) · Springer eBooks · doi:10.1007/0-306-48412-9_8
Dietary factors influencing non-heme iron absorption
Bonsmann, S. S. G. (2007) · Repository for Publications and Research Data (ETH Zurich) · doi:10.3929/ethz-a-005332658
S-NITROSOHEMOGLOBIN: AN ALLOSTERIC MEDIATOR OF NO GROUP FUNCTION IN MAMMALIAN VASCULATURE
Gladwin, M. T., & Patel, R. P. (2004)
Self-citationPlasmodium-Induced Nitrosative Stress in Anopheles stephensi: The Cost of Host Defense
Marie, T., & Peterson, L. (2005) · VTechWorks (Virginia Tech)
Freeman, P. M. (2018) · ORCA Online Research @Cardiff (Cardiff University)
(2004) · Elsevier eBooks · doi:10.1016/b978-044451721-0/50016-5
Bailey, D. M., Bain, A. R., Hoiland, R. L., Barak, O. F., Drviš, I., Stacey, B. S., Iannetelli, A., Davison, G. W., Dahl, R. H., Berg, R. M. G., et al. (2023) · medRxiv · doi:10.1101/2023.07.24.23293124
DeMartino, A. W., Mahan, D. S., Gladwin, B., Correnti, J. E., Xu, Q., Rodriguez, D., Liu, R., Rochon, E. R., Rose, J. J., Kim‐Shapiro, D. B., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104076
Self-citationEfficacy and Safety of Frozen Blood for Transfusion in Trauma Patients - A Multi-Center Trial
Schreiber, M. A., McCully, B. H., Király, L., & Underwood, S. J. (2015)
Investigating the role of nitric oxide clones in cardiovascular conditions
Arif, S. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Metadata
- Authors
- Gladwin, M. T., Wang, X., Reiter, C. D., Yang, B. K., Vivas, E. X., Bonaventura, C., & Schechter, A. N.
- Affiliations
- National Institutes of Health (US)
- Duke University (US)
- Corresponding author
- Gladwin, Mark T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 31
- Pages
- 27818-27828
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2061156310
- Cited by
- 160
- References
- 45
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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
- S-nitrosohemoglobin, nitric oxide storage, erythrocytes, S-nitrosothiols, reductive decomposition, oxygen affinity, allosteric regulation, nitrate formation, redox conditions, nitric oxide delivery
- MeSH terms
- Allosteric Regulation, Animals, Cattle, Drug Stability, Erythrocytes, Hemoglobins, Humans, Kinetics, Nitric Oxide, Nitrites, Oxygen, Serum Albumin, Serum Albumin, Bovine
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