User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo.

Primary tabs

download
  • Open access
  • PDF
  • 680.42 K
Dei Zotti, Flavia [UCL] Lobysheva, Irina [UCL] Balligand, Jean-Luc [UCL]

Reduced bioavailability of nitric oxide (NO) is a major feature of endothelial dysfunction characteristic of cardiovascular and metabolic diseases but the short half-life of NO precludes its easy quantification in circulating blood for early diagnosis. In erythrocytes, NO can react with hemoglobin to form an iron-nitrosyl complex (5-coordinate-α-HbNO) directly quantifiable by Electron Paramagnetic Resonance spectroscopy (EPR) in mouse, rat and human venous blood ex vivo. However, the sources of the nitrosylating species in vivo and optimal conditions of HbNO preservation for diagnostic use in human erythrocytes are unknown. Using EPR spectroscopy, we found that HbNO stability was significantly higher under hypoxia (equivalent to venous pO2; 12.0±0.2% degradation of HbNO at 30 minutes) than at room air (47.7±0.2% degradation) in intact erythrocytes; at 20°C (15.2±0.3% degradation after 30 min versus 29.6±0.1% at 37°C) and under acidic pH (31.7±0.8% versus 62.2±0.4% degradation after 30 min at physiological pH) at 50% of haematocrit. We next examined the relative contribution of NO synthase (NOS) from the vasculature or in erythrocytes themselves as a source of nitrosylating NO. We detected a NOS activity (and eNOS expression) in human red blood cells (RBC), and in RBCs from eNOS(+/+) (but not eNOS(-/-)) mice, as measured by HbNO formation and nitrite/nitrate accumulation. NO formation was increased after inhibition of arginase but abrogated upon NOS inhibition in human RBC and in RBCs from eNOS(+/+) (but not eNOS(-/-)) mice. However, the HbNO signal from freshly drawn venous RBCs was minimally sensitive to the inhibitors ex vivo, while it was enhanced upon caveolin-1 deletion in vivo, suggesting a minor contribution of erythrocyte NOS to HbNO complex formation compared with vascular endothelial NOS or other paracrine NO sources. We conclude that HbNO formation in rodent and human venous erythrocytes is mainly influenced by vascular NO sources despite the erythrocyte NOS activity, so that its measurement by EPR could serve as a surrogate for NO-dependent endothelial function.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2018
Language Anglais
Journal information "PloS one" - Vol. 13, no. 7, p. e0200352 [1-20] (2018)
Peer reviewed yes
Publisher Public Library of Science ((United States) San Francisco, CA)
e-issn 1932-6203
Publication status Publié
Affiliations UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
UCL - (SLuc) Service de médecine interne et maladies infectieuses (MIMI)
Links
  1. Ignarro Louis J., Cirino Giuseppe, Casini Alessandro, Napoli Claudio, Nitric Oxide as a Signaling Molecule in the Vascular System: An Overview : , 10.1097/00005344-199912000-00016
  2. Ghimire Kedar, Altmann Helene M., Straub Adam C., Isenberg Jeffrey S., Nitric oxide: what’s new to NO?, 10.1152/ajpcell.00315.2016
  3. Loscalzo J., Nitric Oxide Insufficiency, Platelet Activation, and Arterial Thrombosis, 10.1161/hh0801.089861
  4. Tousoulis Dimitris, Kampoli Anna-Maria, Tentolouris Nikolaos Papageorgiou Costas, Stefanadis Christodoulos, The Role of Nitric Oxide on Endothelial Function, 10.2174/157016112798829760
  5. Napoli Claudio, Ignarro Louis J., Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases, 10.1007/s12272-009-1801-1
  6. Groves J, Nitric oxide synthase: models and mechanisms, 10.1016/s1367-5931(00)00146-0
  7. Kleinbongard P., Red blood cells express a functional endothelial nitric oxide synthase, 10.1182/blood-2005-10-3992
  8. Cortese-Krott M. M., Rodriguez-Mateos A., Sansone R., Kuhnle G. G. C., Thasian-Sivarajah S., Krenz T., Horn P., Krisp C., Wolters D., Heiss C., Kroncke K.-D., Hogg N., Feelisch M., Kelm M., Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease, 10.1182/blood-2012-07-442277
  9. Yang J., Gonon A. T., Sjoquist P.-O., Lundberg J. O., Pernow J., Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity, 10.1073/pnas.1307058110
  10. Jia Li, Bonaventura Celia, Bonaventura Joseph, Stamler Jonathan S., S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control, 10.1038/380221a0
  11. Gladwin M. T., Ognibene F. P., Pannell L. K., Nichols J. S., Pease-Fye M. E., Shelhamer J. H., Schechter A. N., Relative role of heme nitrosylation and beta -cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation, 10.1073/pnas.180155397
  12. Wood K. C., Cortese-Krott M. M., Kovacic J. C., Noguchi A., Liu V. B., Wang X., Raghavachari N., Boehm M., Kato G. J., Kelm M., Gladwin M. T., Circulating Blood Endothelial Nitric Oxide Synthase Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis, 10.1161/atvbaha.112.301068
  13. Gambaryan Stepan, Subramanian Hariharan, Kehrer Linda, Mindukshev Igor, Sudnitsyna Julia, Reiss Cora, Rukoyatkina Natalia, Friebe Andreas, Sharina Iraida, Martin Emil, Walter Ulrich, Erythrocytes do not activate purified and platelet soluble guanylate cyclases even in conditions favourable for NO synthesis, 10.1186/s12964-016-0139-9
  14. YA Henry, 331 (1997)
  15. Kleschyov Andrei L., Wenzel Philip, Munzel Thomas, Electron paramagnetic resonance (EPR) spin trapping of biological nitric oxide, 10.1016/j.jchromb.2006.10.006
  16. Azizi Fouad, Kielbasa Jerrold E., Adeyiga Adedoyin M., Maree Rachel D., Frazier Matthew, Yakubu Mamudu, Shields Howard, King S. Bruce, Kim–Shapiro Daniel B., Rates of nitric oxide dissociation from hemoglobin, 10.1016/j.freeradbiomed.2005.03.001
  17. Desjardins Fanny, Lobysheva Irina, Pelat Michel, Gallez Bernard, Feron Olivier, Dessy Chantal, Balligand Jean-Luc, Control of blood pressure variability in caveolin-1-deficient mice: role of nitric oxide identified in vivo through spectral analysis, 10.1093/cvr/cvn080
  18. Kirima Kazuyoshi, Tsuchiya Koichiro, Sei Hiroyoshi, Hasegawa Toyoshi, Shikishima Michiyo, Motobayashi Yuki, Morita Kyoji, Yoshizumi Masanori, Tamaki Toshiaki, Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO, 10.1152/ajpheart.01010.2002
  19. Lobysheva Irina I., Biller Pauline, Gallez Bernard, Beauloye Christophe, Balligand Jean-Luc, Nitrosylated Hemoglobin Levels in Human Venous Erythrocytes Correlate with Vascular Endothelial Function Measured by Digital Reactive Hyperemia, 10.1371/journal.pone.0076457
  20. II Lobysheva, Free Radic Biol Med (2017)
  21. Lobysheva I., Rath G., Sekkali B., Bouzin C., Feron O., Gallez B., Dessy C., Balligand J.-L., Moderate Caveolin-1 Downregulation Prevents NADPH Oxidase-Dependent Endothelial Nitric Oxide Synthase Uncoupling by Angiotensin II in Endothelial Cells, 10.1161/atvbaha.111.230623
  22. Ortega Mateo Ana, Amaya Aleixandre de Artiñano M, Nitric oxide reactivity and mechanisms involved in its biological effects, 10.1006/phrs.2000.0701
  23. Siervo M., Stephan B.C.M., Feelisch M., Bluck L.J.C., Measurement of in vivo nitric oxide synthesis in humans using stable isotopic methods: a systematic review, 10.1016/j.freeradbiomed.2011.05.032
  24. Tsikas Dimitrios, Circulating and excretory nitrite and nitrate: Their value as measures of nitric oxide synthesis, bioavailability and activity is inherently limited, 10.1016/j.niox.2015.01.001
  25. Kim-Shapiro Daniel B., Gladwin Mark T., Pitfalls in measuring NO bioavailability using NOx, 10.1016/j.niox.2014.10.003
  26. Gambaryan Stepan, Tsikas Dimitrios, A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from l-arginine or nitrite?, 10.1007/s00726-015-1986-1
  27. Hogg Neil, Detection of nitric oxide by electron paramagnetic resonance spectroscopy, 10.1016/j.freeradbiomed.2010.03.009
  28. Jiang JinJie, Corbett Jean, Hogg Neil, Mason Ronald P., An electron paramagnetic resonance investigation of the oxygen dependence of the arterial–venous gradient of nitrosyl hemoglobin in blood circulation, 10.1016/j.freeradbiomed.2007.06.024
  29. Piknova Barbora, Gladwin Mark T., Schechter Alan N., Hogg Neil, Electron Paramagnetic Resonance Analysis of Nitrosylhemoglobin in Humans during NO Inhalation, 10.1074/jbc.m506292200
  30. Kosaka Hiroaki, Nitric oxide and hemoglobin interactions in the vasculature, 10.1016/s0005-2728(99)00026-2
  31. Yonetani Takashi, Tsuneshige Antonio, Zhou Yuxiang, Chen Xuesi, Electron Paramagnetic Resonance and Oxygen Binding Studies of α-Nitrosyl Hemoglobin : A NOVEL OXYGEN CARRIER HAVING NO-ASSISTED ALLOSTERIC FUNCTIONS, 10.1074/jbc.273.32.20323
  32. Fago Angela, Crumbliss Alvin L., Hendrich Michael P., Pearce Linda L., Peterson Jim, Henkens Robert, Bonaventura Celia, Oxygen binding to partially nitrosylated hemoglobin, 10.1016/j.bbapap.2013.04.017
  33. Stefanovic Marko, Puchulu-Campanella Estela, Kodippili Gayani, Low Philip S., Oxygen regulates the band 3–ankyrin bridge in the human erythrocyte membrane, 10.1042/bj20120869
  34. Oliver S. R., Phillips N. A., Novosad V. L., Bakos M. P., Talbert E. E., Clanton T. L., Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism, 10.1152/ajpregu.00595.2011
  35. Skibba J. L., Powers R. H., Stadnicka A., Cullinane D. W., Almagro U. A., Kalbfleisch J. H., Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia, 10.3109/02656739109056444
  36. Helms Christine, Kim-Shapiro Daniel B., Hemoglobin-mediated nitric oxide signaling, 10.1016/j.freeradbiomed.2013.04.028
  37. Benz Peter M., Fleming Ingrid, Can erythrocytes release biologically active NO?, 10.1186/s12964-016-0145-y
  38. Singel David J., Stamler Jonathan S., CHEMICAL PHYSIOLOGY OF BLOOD FLOW REGULATION BY RED BLOOD CELLS: : The Role of Nitric Oxide and S-Nitrosohemoglobin, 10.1146/annurev.physiol.67.060603.090918
  39. Cortese-Krott Miriam M., Mergia Evanthia, Kramer Christian M., Lückstädt Wiebke, Yang Jiangning, Wolff Georg, Panknin Christina, Bracht Thilo, Sitek Barbara, Pernow John, Stasch Johannes-Peter, Feelisch Martin, Koesling Doris, Kelm Malte, Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease, 10.1016/j.redox.2017.08.020
  40. Angermeier E., Domes K., Lukowski R., Schlossmann J., Rathkolb B., Angelis M. H., Hofmann F., Iron deficiency anemia in cyclic GMP kinase knockout mice, 10.3324/haematol.2015.137026
  41. Foller M., Feil S., Ghoreschi K., Koka S., Gerling A., Thunemann M., Hofmann F., Schuler B., Vogel J., Pichler B., Kasinathan R. S., Nicolay J. P., Huber S. M., Lang F., Feil R., Anemia and splenomegaly in cGKI-deficient mice, 10.1073/pnas.0708940105
  42. Kuhn Viktoria, Diederich Lukas, Keller T.C. Stevenson, Kramer Christian M., Lückstädt Wiebke, Panknin Christina, Suvorava Tatsiana, Isakson Brant E., Kelm Malte, Cortese-Krott Miriam M., Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia, 10.1089/ars.2016.6954
  43. V Barodka, Transfusion, 54, 434 (2014)
  44. Belanger Andrea M., Keggi Christian, Kanias Tamir, Gladwin Mark T., Kim-Shapiro Daniel B., Effects of nitric oxide and its congeners on sickle red blood cell deformability : SNP IMPROVES SICKLE RBC DEFORMABILITY, 10.1111/trf.13134
  45. Diederich Lukas, Suvorava Tatsiana, Sansone Roberto, Keller T. C. Stevenson, Barbarino Frederik, Sutton Thomas R., Kramer Christian M., Lückstädt Wiebke, Isakson Brant E., Gohlke Holger, Feelisch Martin, Kelm Malte, Cortese-Krott Miriam M., On the Effects of Reactive Oxygen Species and Nitric Oxide on Red Blood Cell Deformability, 10.3389/fphys.2018.00332
  46. Vaughn Mark W., Huang Kuang-Tse, Kuo Lih, Liao James C., Erythrocytes Possess an Intrinsic Barrier to Nitric Oxide Consumption, 10.1074/jbc.275.4.2342
  47. Steven Sebastian, Dib Mobin, Roohani Siyer, Kashani Fatemeh, Münzel Thomas, Daiber Andreas, Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia—A Comparative Study of Mice and Rats, 10.3390/ijms18102176
  48. Li Haitao, Liu Xiaoping, Cui Hongmei, Chen Yeong-Renn, Cardounel Arturo J., Zweier Jay L., Characterization of the Mechanism of Cytochrome P450 Reductase-Cytochrome P450-mediated Nitric Oxide and Nitrosothiol Generation from Organic Nitrates, 10.1074/jbc.m511803200
  49. Daiber Andreas, Münzel Thomas, Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress, 10.1089/ars.2015.6376
Bibliographic reference Dei Zotti, Flavia ; Lobysheva, Irina ; Balligand, Jean-Luc. Nitrosyl-hemoglobin formation in rodent and human venous erythrocytes reflects NO formation from the vasculature in vivo.. In: PloS one, Vol. 13, no. 7, p. e0200352 [1-20] (2018)
Permanent URL http://hdl.handle.net/2078.1/200906