Oxidative pathways in the sickle cell and beyond

Blood Cells, Molecules, and Diseases

Volumn 70, Issue , 2018, Pages 78-86

  Alayash, Abdu I ^a  

^a CENTER FOR BIOLOGICS EVALUATION AND RESEARCH   (United States)

Author keywords

Ferryl hemoglobin; Heme oxidation; Microparticles; Pseudoperoxidase; Sickle cell hemoglobin

Indexed keywords

ASCORBIC ACID; BLOOD SUBSTITUTE; CARBON MONOXIDE; HEME; HEMOGLOBIN; HEMOGLOBIN S; HEMOPEXIN; HYDROXYUREA; NITRIC OXIDE; OXYGEN; PEROXIDASE; REACTIVE OXYGEN METABOLITE; ANTIOXIDANT;

AUTOOXIDATION; BLOOD VESSEL OCCLUSION; CYTOSOL; DISEASE COURSE; DISEASE EXACERBATION; ENZYME MECHANISM; ERYTHROCYTE; EXTRACELLULAR MATRIX; HEMOLYSIS; HUMAN; INFLAMMATION; METABOLIC RATE; METABOLIC REGULATION; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; OXYGEN TRANSPORT; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN POLYMERIZATION; PULMONARY HYPERTENSION; REVIEW; SICKLE CELL; SICKLE CELL TRAIT; STEADY STATE; VASCULAR DISEASE; BLOOD; ERYTHROCYTE DISORDER; GENETICS; MEMBRANE MICROPARTICLE; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY; SICKLE CELL ANEMIA;

ANEMIA, SICKLE CELL; ANTIOXIDANTS; BLOOD SUBSTITUTES; CELL-DERIVED MICROPARTICLES; ERYTHROCYTES; ERYTHROCYTES, ABNORMAL; HEME; HEMOGLOBIN, SICKLE; HUMANS; METABOLIC NETWORKS AND PATHWAYS; OXIDATION-REDUCTION; OXIDATIVE STRESS; PEROXIDASE;

EID: 85019887690     PISSN: 10799796     EISSN: 10960961     Source Type: Journal    
DOI: 10.1016/j.bcmd.2017.05.009     Document Type: Review

References (101)

1. Pauling, L., Itano, H.A., Singer, S.J., Wells, I.C., Sickle cell anemia, a molecular disease. Science 110 (1949), 543–548.
2. Dickerson, R.E., Gies, I., Hemoglobin: Structure, Function, Evolution, and Pathology. 1983, The Benjamin/Cummings Publishing Company, California.
3. Hebbel, R.P., Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol. Oncol. Clin. North Am. 28 (2014), 181–198.
4. Wood, K.C., Granger, D.N., Sickle cell disease: role for reactive oxygen and nitrogen metabolites. Clin. Exp. Pharm. Physiol 34 (2007), 926–932.
5. Connes, P.I., Lamarre, Y., Waltz, X., Ballas, S.K., Lemonne, N. et al., Haemolysis and abnormal haemorheology in sickle cell anaemia. Br. J. Haematol 165 (2014), 564–572.
6. Ghosh, S., Adisa, O.A., Chappa, P., Tan, F., Jackson, K.A. et al., Extracellular hemin crisis triggers acute chest syndrome in sickle mice. J. Clin. Invest. 123 (2013), 4809–4820.
7. Schaer, D.J., Buehler, P.W., Alayash, A.I., Belcher, D.J., Vercellotti, G.M., Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood 121 (2013), 1276–1284.
8. Hebbel, R.P., Morgan, W.T., Eaton, J.W., Hedlund, B.E., Accelerated autoxidation and heme loss due to instability of sickle hemoglobin. Proc. Natl. Acad. Sci. U. S. A. 85 (1988), 237–241.
9. Kuypers, F.A., Hemoglobin S polymerization and red cell membrane changes. Hematol. Oncol. Clin. N. Am. 28 (2014), 155–179.
10. Silverman, T.A., Weiskopf, R.B., Hemoglobin-based oxygen carriers: current status and future directions. Transfusion 49 (2009), 2495–2515.
11. Buehler, P.W., D'Agnillo, F., Schaer, D.J., Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design. Trends Mol. Med. 10 (2010), 447–457.
12. Alayash, A.I., Setbacks in blood substitutes research and development: a biochemical perspective. Clin. Lab. Med. 30 (2010), 381–389.
13. Weiskopf, R.B., Hemoglobin-based oxygen carriers: disclosed history and the way ahead: the relativity of safety. Anesth. Analg. 119 (2014), 758–760.
14. Winslow, R.M., Oxygen: the poison is in the dose. Transfusion 53 (2013), 424–437.
15. Alayash, A.I., Oxygen therapeutics: can we tame haemoglobin?. Nat. Rev. Drug Discov. 3 (2004), 152–159.
16. Buehler, P.W., D'Agnillo, F., Hoffman, V., Alayash, A.I., Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig. J. Pharmacol. Exp. Ther. 323 (2007), 49–60.
17. Reeder, B.J., The redox activity of hemoglobins: from physiologic functions to pathologic mechanisms. Antioxid. Redox Signal. 13 (2010), 1087–1123.
18. Jia, Y., Buehler, P.W., Boykins, R.A., Venable, R.M., Alayash, A.I., Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway. J. Biol. Chem. 282 (2007), 4894–4907.
19. Kassa, T., Jana, S., Strader, M.B., Meng, F., Jia, Y. et al., Sickle Cell Hemoglobin in the ferryl state promotes βCys-93 oxidation and mitochondrial dysfunction in epithelial lung cells (E10). J. Biol. Chem. 290 (2015), 27939–27958.
20. Kassa, T., Jana, S., Meng, F., Alayash, A.I., Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase-1. FEBS Open Bio. 6 (2016), 876–884.
21. Bonaventura, C., Henkens, R., Alayash, A.I., Crumbliss, A.L., Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobins. IUBMB Life 59 (2007), 498–505.
22. Nagababu, E., Ramasamy, S., Rifkind, J.M., Jia, Y., Alayash, A.I., Site-specific cross-linking of human and bovine hemoglobins differentially alters oxygen binding and redox side reactions producing rhombic heme and heme degradation. Biochemistry 41 (2002), 7407–7415.
23. Bonaventura, C., Henkens, R., Alayash, A.I., Banerjee, S., Crumbliss, A.L., Molecular controls of the oxygenation and redox reactions of hemoglobin. Antioxid. Redox Signal. 18 (2013), 2298–2313.
24. Mollan, T.L., Jia, Y., Banerjee, S., Wu, G., Kreulen, R.T. et al., Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin. Free Radic. Biol. Med. 69 (2014), 265–277.
25. Vandegriff, K.D., Malavalli, A., Minn, C., Jiang, E., Lohman, J. et al., Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates. Biochem. J. 3 (2006), 463–471.
26. Lee, R., Neya, K., Svizzero, T.A., Vlahakes, G.J., Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions. J. Appl. Physiol. 79 (1985), 236–242.
27. Manalo, D.J., Buehler, P.W., Baek, J.H., Butt, O., D'Agnillo, F. et al., Acellular haemoglobin attenuates hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes in haemodiluted rats. Biochem. J. 414 (2008), 461–469.
28. Rentsendorj, O., Zhang, X., Williams, M.C., Buehler, P.W., D'Agnillo, F., Transcriptional suppression of renal antioxidant enzyme systems in guinea pigs exposed to polymerized cell-free hemoglobin. Toxics, 4, 2016 (pii: 6. Epub 2016 Feb 19).
29. Baek, J.H., D'Agnillo, F., Vallelian, F., Pereira, C.P., Williams, M.C. et al., Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy. J. Clin. Invest. 122 (2012), 1444–1458.
30. Fitzgerald, M.C., Chan, J.Y., Ross, A.W., Liew, S.M., Butt, W.W. et al., A synthetic haemoglobin-based oxygen carrier and the reversal of cardiac hypoxia secondary to severe anaemia following trauma. Med. J. Aust. 194 (2011), 471–473.
31. Hebbel, R.P., Ney, P.A., Foker, W., Autoxidation, dehydration, and adhesivity may be related abnormalities of sickle erythrocytes. Am. J. Phys. 56 (1989), C579–C583.
32. Marva, E., Hebbel, R.P., Denaturing interaction between sickle hemoglobin and phosphatidylserine liposomes. Blood 83 (1994), 242–249.
33. Chirico, E.N., Pialoux, V., Role of oxidative stress in the pathogenesis of sickle cell disease. IUBMB Life 64 (2012), 72–80.
34. George, A., Pushkaran, S., Konstantinidis, D.G., Koochaki, S., Malik, P. et al., Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood 121 (2013), 2099–2109.
35. Gizi, A., Papassotiriou, I., Apostolakou, F., Lazaropoulou, C., Papastamataki, M. et al., Assessment of oxidative stress in patients with sickle cell disease: the glutathione system and the oxidant–antioxidant status. Blood Cells Mol. Dis. 46 (2011), 220–225.
36. 2 content, glycolysis, and antioxidant capacity. Blood 121 (2013), 1651–1662.
37. Cyrklaff, M., Sanchez, C.P., Kilian, N., Bisseye, C., Simpore, J. et al., Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science 334 (2011), 1283–1286.
38. Nur, E., Brandjes, D.P., Schnog, J.J., HM, HOtten, Fijnvandraat, K. et al., Plasma levels of advanced glycation end products are associated with haemolysis-related organ complications in sickle cell patients. Br. J. Haematol. 151 (2010), 62–69.
39. Hierso, R., Lemonne, N., Villaescusa, R., Lalanne-Mistrih, M.-L., Charlot, K., Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study. Br. J. Haematol., 2016, 10.1111/bjh.14476 (Dec 16, Epub ahead of print).
40. Silva, D.G.H., Belini, E. Jr., Alves de Almeida, E., Regina Bonini-Domingos, C.C.R., Oxidative stress in sickle cell disease: an overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies. Free Rad. Biol. Med. 65 (2013), 1101–1109.
41. Stubbe, J., Riggs-Gelasco, P., Harnessing free radicals: formation and function of the tyrosyl radical in ribonucleotide reductase. TIBS 23 (1998), 434–443.
42. Belcher, J.D., Chen, C., Nguyen, J., Milbauer, L., Abdulla, F. et al., Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 123 (2014), 377–390.
43. Adisa, O.A., Yijuan, H., Ghosh, S., Aryee, D., Ifeyinwa, O. et al., Association between plasma free haem and incidence of vasoocclusive episodes and acute chest syndrome in children with sickle cell disease. Br. J. Haematol. 162 (2013), 702–705.
44. Allan, D., Limbrick, A.R., Thomas, P., Westerman, M.P., Release of spectrin-free spicules on reoxygenation of sickled erythrocytes. Nature 295 (1982), 612–613.
45. Willekens, F.L., Werre, J.M., Kruijt, J.K., Roerdin-kholder-Stoelwinder, B., Groenen-Dopp, Y.A. et al., Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood 105 (2005), 2141–2145.
46. Hebbel, R.P., Key, N.S., Microparticles in sickle cell anaemia: promise and pitfalls. Br. J. Haem. 174 (2016), 16–29.
47. Vercellotti, G.M., Special delivery: microparticles convey heme. Blood 125 (2015), 3677–3678.
48. Azarov, I., Liu, C., Reynolds, H., Tsekouras, Z., Lee, J.S. et al., Mechanisms of slower nitric oxide uptake by red blood cells and other hemoglobin-containing vesicles. J. Biol. Chem. 286 (2011), 33567–33579.
49. Camus, S.M., De Moraes, J.O., Bonnin, P., Abbyad, P., Le Jeune, S. et al., Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease Lambry,3 Dominique Charue. Blood 125 (2015), 3805–3814.
50. Wicher, K., Fries, E., Evolutionary aspects of hemoglobin scavenger. Antioxid. Redox Signal. 12 (2010), 249–259.
51. Langlois, M.R., Delanghe, J.R., Biological and clinical significance of haptoglobin polymorphism in humans. Clin. Chem. 42 (1996), 589–600.
52. Alayash, A.I., Haptoglobin: old protein with new functions. Clin. Chim. Acta 412 (2011), 493–498.
53. Alayash, A.I., Andersen, C.B., Moestrup, S.K., Bülow, L., Haptoglobin: the hemoglobin detoxifier in plasma. Trends Biotechnol. 31 (2013), 2–3.
54. Reeder, B.J., Grey, M., Silaghi-Dumitrescu, R.L., Svistunenko, D.A., Bülow, L. et al., Tyrosine residues as redox cofactors in human hemoglobin: implications for engineering nontoxic blood substitutes. J. Biol. Chem 283 (2008), 30780–33087.
55. Cooper, C.E., Schaer, D.J., Buehler, P.W., Wilson, M.T., Reeder, B.J., Haptoglobin binding stabilizes hemoglobin ferryl iron and the globin radical on tyrosine β145. Antioxid. Redox Signal. 18 (2013), 2264–2267.
56. Smith, A., McCulloh, R.J., Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol., 6, 2015, 187, 10.3389/fphys.2015.00187.
57. Buehler, P.W., Karnaukhova, E., Gelderman, M.P., Alayash, A.I., Blood aging, safety, and transfusion: capturing the “radical” menace. Antioxid. Redox Signal. 14 (2011), 1713–1728.
58. Paoli, M., Anderson, B.F., Baker, H.M., Morgan, W.T., Smith, A. et al., Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains. Nat. Struct. Biol. 6 (1999), 926–931.
59. Hrkal, Z., Vodrázka, Z., Kalousek, I., Transfer of heme from ferrihemoglobin and ferrihemoglobin isolated chains to hemopexin. Eur. J. Biochem. 43 (1974), 73–78.
60. Vercellotti, G.M., Zhang, P., Nguyen, J., Abdulla, F., Chen, C. et al., Overexpression of hemopexin inhibits inflammation and vascular stasis in murine models of sickle cell disease. Mol. Med. 22 (2016), 437–451.
61. Schaer, D.J., Buehler, P.W., Cell-free hemoglobin and its scavenger proteins: new disease models leading the way to targeted therapies. Cold Spring Harb. Perspect. Med., 3(6 or replace), 2013 (Jun 1).
62. Chintagari, N.R., Nguyen, J., Belcher, J.D., Vercellotti, G.M., Alayash, A.I., Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease. Blood Cells Mol. Dis. 54 (2015), 302–306.
63. Shi, P.A., Choi, E., Chintagari, N.R., Nguyen, J., Guo, X. et al., Sustained treatment of sickle cell mice with haptoglobin increases HO-1 and H-ferritin expression and decreases iron deposition in the kidney without improvement in kidney function. Br. J. Haematol. 175 (2016), 714–723.
64. Amer, J., Ghoti, H., Rachmilewitz, E., Koren, A., Levin, C. et al., Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br. J. Haematol. 132 (2006), 108–113.
65. Marangon, K., Devaraj, S., Tirosh, O., Packer, L., Jialal, I., Comparison of the effect of α-lipoic acid and α-tocopherol supplementation on measures of oxidative stress. Free Radic. Biol. Med. 27 (1999), 1114–1121.
66. Arruda, M.M., Mecabo, G., Rodrigues, C.A., Matsuda, S.S., Rabelo, I.B. et al., Antioxidant vitamins C and E supplementation increases markers of haemolysis in sickle cell anaemia patients: a randomized, double-blind, placebo-controlled trial. Br. J. Haematol. 160 (2013), 688–700.
67. Muskiet, F.A., Muskiet, F.D., Meiborg, G., Schermer, J.G., Supplementation of patients with homozygous sickle cell disease with zinc, alpha-tocopherol, vitamin C, soybean oil, and fish oil. Am. J. Clin. Nutr. 54 (1991), 736–744.
68. Dunne, J., Caron, A., Menu, P., Alayash, A.I., Buehler, P.W. et al., Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo. Biochem. J. 399 (2006), 513–524.
69. Cooper, C.E., Silaghi-Dumitrescu, R., Rukengwa, M., Alayash, A.I., Buehler, P.W., Peroxidase activity of hemoglobin towards ascorbate and urate: a synergistic protective strategy against toxicity of Hemoglobin-Based Oxygen Carriers (HBOC). Biochim. Biophys. Acta 1784 (2008), 1415–1420.
70. Silkstone, G.G., Silkstone, R.S., Wilson, M.T., Simons, M., Bülow, L. et al., Engineering tyrosine electron transfer pathways decreases oxidative toxicity in hemoglobin: implications for blood substitute design. Biochem. J. 473 (2016), 3371–3383.
71. Kato, G.J., New insights into sickle cell disease: mechanisms and investigational therapies. Curr. Opin. Hematol. 23 (2016), 224–232.
72. Steinberg, M.H., Lu, Z.H., Barton, F.B., Terrin, M.L., Charache, S., Dover, G.J., Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood 89 (1997), 1078–1088.
73. Ferrone, F.A., Sickle cell disease: its molecular mechanism and the one drug that treats it. Inter. J. Biol. Macromol 93 (2016), 1168–1173.
74. Silva, D.G., Belini, E. Jr., Torres Lde, S., Ricci, O. Jr., Lobo, C. et al., Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia. Blood Cells Mol. Dis 47 (2011), 23–28.
75. Vankayala, S.L., Hargis, J.C., Woodcock, H.L., Unlocking the binding and reaction mechanism of hydroxyurea substrates as biological nitric oxide donors. J. Chem. Inf. Model. 52 (2012), 1288–1297.
76. Araujo, J.A., HO-1 and CO: fighters vs sickle cell disease?. Blood 122 (2013), 2535–2536.
77. Alayash, A.I., Hemoglobin-based blood substitutes and the treatment of sickle cell disease: more harm than help?. Biomolecules, 7, 2017, 10.3390/biom7010002 (pii: E2).
78. Winslow, R.M., MP4, a new nonvasoactive polyethylene glycol-hemoglobin conjugate. Artif. Organs 9 (2004), 800–806.
79. Olofsson, C.I., Górecki, A.Z., Dirksen, R., Kofranek, I., Majewski, J.A. et al., Evaluation of MP4OX for prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology 114 (2011), 1048–1063.
80. Vandegriff, K.D., Young, M.A., Lohman, J., Bellelli, A., Samaja, M. et al., CO-MP4, a polyethylene glycol-conjugated haemoglobin derivative and carbon monoxide carrier that reduces myocardial infarct size in rats. Br. J. Pharmacol. 154 (2008), 1649–1661.
81. Belcher, J.D., Young, M., Chen, C., Nguyen, J., Burhop, K. et al., MP4CO, a pegylated hemoglobin saturated with carbon monoxide, is a modulator of HO-1, inflammation, and vaso-occlusion in transgenic sickle mice. Blood 122 (2013), 2757–2764.
82. Nho, K., Glower, D., Bredehoeft, S., Shankar, H., Shorr, R. et al., PEG-bovine hemoglobin: safety in a canine dehydrated hypovolemic-hemorrhagic shock model. Biomater. Artif. Cells Immobil. Biotechnol. 20 (1992), 511–524.
83. Zhang, J., Cao, S., Kwansa, H., Crafa, D., Kibler, K.K. et al., Transfusion of hemoglobin-based oxygen carriers in the carboxy state is beneficial during transient focal cerebral ischemia. J. Appl. Physiol. 113 (2012), 1709–1717.
84. Abuchowski, A., PEGylated bovine Carboxyhemoglobin (SANGUINATE™): results of clinical safety testing and use in patients. Adv. Exp. Med. Biol. 876 (2016), 461–467.
85. Zhang, R., Hess, D.T., Qian, Z., Hausladen, A., Fonseca, F. et al., Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia. Proc. Natl. Acad. Sci. USA 112 (2015), 6425–6430.
86. Kim-Shapiro, D.B., Gladwin, M.T., Mechanisms of nitrite bioactivation. Nitric Oxide 38 (2014), 58–68.
87. Bunn, H.F., Nathan, D.G., Dover, G.J., Hebbel, R.P., Platt, O.S. et al., Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood 116 (2010), 687–692.
88. Moon-Massat, P., Scultetus, A., Arnaud, F., Brown, A., Haque, A. et al., Effect of HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine. Injury 43 (2012), 638–647.
89. Baek, J.H., Zhang, X., Williams, M.C., Hicks, W., Buehler, P.W. et al., Sodium nitrite potentiates renal oxidative stress and injury in hemoglobin exposed guinea pigs. Toxicology 333 (2015), 89–99.
90. Kato, G.J., M.H. Steinberg MH, M.T. Gladwin MT., Intravascular hemolysis and the pathophysiology of sickle cell disease. J. Clin. Invest. 127 (2017), 750–760.
91. Machado, R.F., Barst, R.J., Yovetich, N.A., Hassell, K.L., Kato, G.J. et al., Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood 118 (2011), 855–864.
92. Head, A., Brugnara, C., Martinez-Ruiz, R., Kacmarek, R.M., Kenneth, R. et al., Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo. J. Clin. Invest. 100 (1997), 1193–1198.
93. Rossaint, O.R., Lewandowski, K., Zapol, W.M., Our paper 20 years later: inhaled nitric oxide for the acute respiratory distress syndrome—discovery, current understanding, and focused targets of future applications. Intensive Care Med 40 (2014), 1649–1658.
94. Keszler, A., Piknova, B., Schechter, A.N., Hogg, N., The reaction between nitrite and oxyhemoglobin: a mechanistic study. J. Biol. Chem. 283 (2008), 9615–9622.
95. Hrinczenko, B.W., Alayash, A.I., Wink, D.A., Gladwin, M.T., Rodgers, G.P. et al., Effect of nitric oxide and nitric oxide donors on red blood cell oxygen transport. Br. J. Haematol 110 (2000), 412–419.
96. Hrinczenko, B.W., Schechter, A.N., Wojtkowski, T.L., Pannell, L.K., Cashon, R.E. et al., Nitric oxide-mediated heme oxidation and selective beta-globin nitrosation of hemoglobin from normal and sickle erythrocytes. Biochem. Biophys. Res. Commun. 275 (2000), 962–967.
97. Gorbunov, N.V., Osipov, A.N., Day, B.W., Zayas-Rivera, B., Kagan, V.E. et al., Reduction of ferrylmyoglobin and ferrylhemoglobin by nitric oxide: a protective mechanism against ferryl hemoprotein-induced oxidations. Biochemistry 34 (1995), 6689–6699.
98. Strader, M.B., Kassa, T., Meng, F., Wood, F.B., Hirsch, R.E. et al., Oxidative instability of hemoglobin E (β26 Glu → Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): relevance to HbE/β-thalassemia. Redox Biol. 8 (2016), 363–374.
99. Nakagawa, A., Lui, F.E., Wassaf, D., Yefidoff-Freedman, R., Dominick, C. et al., Identification of a small molecule that increases hemoglobin oxygen affinity and reduces SS erythrocyte sickling. ACS Chem. Biol. 9 (2014), 2318–2325.
100. Lia, Q., Henry, R.E.R., Hofrichter, J., Jeffrey, F., Smith, F. et al., Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease. Proc. Natl. Acad. Sci. U S A 114 (2017), E689–E696.
101. Eaton, W.A., Bunn, H.F., Treating sickle cell disease by targeting HbS polymerization. Blood, 2017 pii: blood-2017-02-765891 10.1182/blood-2017-02-765891 (Apr 6, Epub ahead of print).