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Biochemistry (Moscow)

, Volume 83, Issue 12–13, pp 1575–1593 | Cite as

Alternate and Additional Functions of Erythrocyte Hemoglobin

  • O. V. Kosmachevskaya
  • A. F. TopunovEmail author
Review
  • 58 Downloads

Abstract

The review discusses pleiotropic effects of erythrocytic hemoglobin (Hb) and their significance for human health. Hemoglobin is mostly known as an oxygen carrier, but its biochemical functions are not limited to this. The following aspects of Hb functioning are examined: (i) catalytic functions of the heme component (nitrite reductase, NO dioxygenase, monooxygenase, alkylhydroperoxidase) and of the apoprotein (esterase, lipoxygenase); (ii) participation in nitric oxide metabolism; (iii) formation of membrane–bound Hb and its role in the regulation of erythrocyte metabolism; (iv) physiological functions of Hb catabolic products (iron, CO, bilirubin, peptides). Special attention is given to Hb participation in signal transduction in erythrocytes. The relationships between various erythrocyte metabolic parameters, such as oxygen status, ATP formation, pH regulation, redox balance, and state of the cytoskeleton are discussed with regard to Hb. Hb polyfunctionality can be considered as a manifestation of the principle of biochemical economy.

Keywords

hemoglobin erythrocytes membrane–bound hemoglobin nitric oxide capillary blood flow peroxidase activity heme 

Abbreviations

Band3

band 3 protein

CDB3

cytoplasmic domain of band 3 protein

DNIC

dinitrosyl iron complexes

Fgb

flavohemoglobin

Hb

hemoglobin

Hp

haptoglobin

MBHb

membrane–bound hemoglobin

NOD reaction

NO dioxygenase reaction

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References

  1. 1.
    Tejero, J., and Gladwin, M. T. (2014) The globin superfamily: functions in nitric oxide formation and decay, Biol. Chem., 395, 631–639.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kosmachevskaya, O. V., and Topunov, A. F. (2009) Hemoglobins: diversity of structures and functions, Appl. Biochem. Microbiol., 45, 563–587.CrossRefGoogle Scholar
  3. 3.
    Vinogradov, S. N., and Moens, L. (2008) Diversity of globin function: enzymatic, transport, storage and sensing, J. Biol. Chem., 283, 8773–8777.PubMedGoogle Scholar
  4. 4.
    Palmer, R. M., Ferrige, A. G., and Moncada, S. (1987) Nitric oxide release accounts for the biological activity of endothelium–derived relaxing factor, Nature, 327, 524–526.CrossRefPubMedGoogle Scholar
  5. 5.
    Hill, B. G., Dranka, B. P., Bailey, S. M., Lancaster, J. R., Jr., and Darley–Usmar, V. M. (2010) What part of NO don’t you understand? Some answers to the cardinal questions in nitric oxide biology, J. Biol. Chem., 285, 19699–19704.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Vinogradov, S. N., Fernandez, I., Hoogewijs, D., and Arredondo–Peter, R. (2011) Phylogenetic relationships of 3/3 and 2/2 hemoglobins in Archaeplastida genomes to bacterial and other eukaryote hemoglobins, Mol. Plant., 4, 42–58.CrossRefPubMedGoogle Scholar
  7. 7.
    Gardner, P. R. (2005) Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases, J. Inorg. Biochem., 99, 247–266.PubMedGoogle Scholar
  8. 8.
    Perazzolli, M., Dominici, P., Romero–Puertas, M. C., Zago, E., Zeier, J., Sonoda, M., Lamb, C., and Delledonne, M. (2004) Arabidopsis nonsymbiotic hemoglobin AHb1 modulates nitric oxide bioactivity, Plant Cell., 16, 2785–2794.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gardner, A. M., Cook, M. R., and Gardner, P. R. (2010) Nitric–oxide dioxygenase function of human cytoglobin with cellular reductants and in rat hepatocytes, J. Biol. Chem., 285, 23850–23857.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Jia, L., Bonaventura, C., Bonaventura, J., and Stamler, J. S. (1996) S–nitrosohaemoglobin: a dynamic activity of blood involved in vascular control, Nature, 380, 221–226.CrossRefPubMedGoogle Scholar
  11. 11.
    Doctor, A., Platt, R., Sheram, M. L., Eischeid, A., McMahon, T., Maxey, T., Doherty, J., Axelrod, M., Kline, J., Gurka, M., Gow, A., and Gaston, B. (2005) Hemoglobin conformation couples erythrocyte S–nitrosothiol content to O2 gradients, Proc. Natl. Acad. Sci. USA, 102, 5709–5714.CrossRefPubMedGoogle Scholar
  12. 12.
    Timoshin, A. A., Vanin, A. F., Orlova, Ts. R., Sanina, N. A., Ruuge, E. K., Aldoshin, S. M., and Chazov, E. I. (2007) Protein–bound dinitrosyl–iron complexes appearing in blood of rabbit added with a low–molecular dinitrosyl–iron complexes: EPR studies, Nitric Oxide, 16, 286–293.CrossRefPubMedGoogle Scholar
  13. 13.
    Shumaev, K. B., Gubkin, A. A., Serezhenkov, V. A., Lobysheva, I. I., Kosmachevskaya, O. V., Ruuge, E. K., Lankin, V. Z., Topunov, A. F., and Vanin, A. F. (2008) Interaction of reactive oxygen and nitrogen species with albumin–and hemoglobin–bound dinitrosyl iron complexes, Nitric Oxide, 18, 37–46.CrossRefPubMedGoogle Scholar
  14. 14.
    Shumaev, K. B., Kosmachevskaya, O. V., Timoshin, A. A., Vanin, A. F., and Topunov, A. F. (2008) Dinitrosyl iron complexes bound with haemoglobin as markers of oxidative stress, Methods Enzymol., 436, 445–461.CrossRefPubMedGoogle Scholar
  15. 15.
    Gow, A. J., and Stamler, J. S. (1998) Reactions between nitric oxide and haemoglobin under physiological conditions, Nature, 391, 169–173.CrossRefPubMedGoogle Scholar
  16. 16.
    Herold, S., Exner, M., and Nauser, T. (2001) Kinetic and mechanistic studies of the NO•–mediated oxidation of oxymyoglobin and oxyhemoglobin, Biochemistry, 40, 3385–3395.CrossRefPubMedGoogle Scholar
  17. 17.
    Cortese–Krott, M. M., and Kelm, M. (2014) Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol., 2, 251–258.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Stamler, J. S. (2004) S–Nitrosothiols in the blood roles, amounts, and methods of analysis, Circ. Res., 94, 414–417.PubMedGoogle Scholar
  19. 19.
    Stamler, J. S., Singel, D. J., and Piantadosi, C. A. (2008) SNO–hemoglobin and hypoxic vasodilation, Nat. Med., 14, 1008–1009.CrossRefPubMedGoogle Scholar
  20. 20.
    Benesch, R. E., and Benesch, R. (1962) The influence of oxygenation on the reactivity of the–SH groups of hemoglobin, Biochemistry, 1, 735–738.CrossRefPubMedGoogle Scholar
  21. 21.
    Sandalova, T. P., and Ignatenko, T. V. (1984) Oxidation Hemoglobin with Modified SH–Groups [in Russian], Siberian Branch of the USSR Academy of Sciences, L. V. Kirensky Institute of Physics, Krasnoyarsk, Preprint No. 308F.Google Scholar
  22. 22.
    Doyle, M. P., Pickering, R. A., DeWeert, T. M., Hoekstra, J. W., and Pater, D. (1981) Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites, J. Biol. Chem., 256, 12393–12398.PubMedGoogle Scholar
  23. 23.
    Huang, K. T., Keszler, A., Patel, N., Patel, R. P., Gladwin, M. T., Kim–Shapiro, D. B., and Hogg, N. (2005) The reaction between nitrite and deoxyhemoglobin. Reassessment of reaction kinetics and stoichiometry, J. Biol. Chem., 280, 31126–31131.CrossRefPubMedGoogle Scholar
  24. 24.
    Helms, C., and Kim–Shapiro, D. B. (2013) Hemoglobin–mediated nitric oxide signaling, Free Radic. Biol. Med., 61, 464–472.CrossRefPubMedGoogle Scholar
  25. 25.
    Gladwin, M. T., Grubina, R., and Doyle, M. P. (2009) The new chemical biology of nitrite reactions with hemoglobin: R–state catalysis, oxidative denitrosylation, and nitrite reductase/anhydrase, Acc. Chem. Res., 42, 157–167.PubMedGoogle Scholar
  26. 26.
    Cantu–Medellin, N., Vitturi, D. A., Rodriguez, C., Murphy, S., Dorman, S., Shiva, S., Zhou, Y., Jia, Y., Palmer, A. F., and Patel, R. P. (2011) Effects of T–state and R–state stabilization on deoxyhemoglobin–nitrite reactions and stimulation of nitric oxide signaling, Nitric Oxide, 25, 59–69.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Keszler, A., Piknova, B., Schechter, A. N., and Hogg, N. (2008) The reaction between nitrite and oxyhemoglobin: a mechanistic study, J. Biol. Chem., 283, 9615–9622.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Zavodnik, I. B., Lapshina, E. A., Rekawiecka, K., Zavodnik, L. B., Bartosz, G., and Bryszewska, M. (1999) Membrane effects of nitrite–induced oxidation of human red blood cells, Biochim. Biophys. Acta, 1421, 306–316.CrossRefPubMedGoogle Scholar
  29. 29.
    Nagababu, E., and Rifkind, J. M. (2007) Measurement of plasma nitrite by chemiluminescence without interference of S–, N–nitroso and nitrated species, Free Radic. Biol. Med., 42, 1146–1154.CrossRefPubMedGoogle Scholar
  30. 30.
    Nagababu, E., Ramasamy, S., Abernethy, D. R., and Rifkind, J. M. (2003) Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin–mediated nitrite reduction, J. Biol. Chem., 278, 46349–46356.CrossRefPubMedGoogle Scholar
  31. 31.
    Gladwin, M. T., Raat, N. J., Shiva, S., Dezfulian, C., Hogg, N., Kim–Shapiro, D. B., and Patel, R. P. (2006) Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation, Am. J. Physiol. Heart Circ. Physiol., 291, 2026–2035.CrossRefGoogle Scholar
  32. 32.
    Shiva, S. (2013) Nitrite: a physiological store of nitric oxide and modulator of mitochondrial function, Redox Biol., 1, 40–44.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Dalsgaard, T., Simonsen, U., and Fago, A. (2007) Nitrite–dependent vasodilation is facilitated by hypoxia and is independent of known NO–generating nitrite reductase activities, Am. J. Physiol. Heart. Circ. Physiol., 292, 3072–3078.CrossRefGoogle Scholar
  34. 34.
    Crawford, J. H., Isbell, T. S., Huang, Z., Shiva, S., Chacko, B. K., Schechter, A. N., Darley–Usmar, V. M., Kerby, J. D., Lang, J. D., Jr., Kraus, D., Ho, C., Gladwin, M. T., and Patel, R. P. (2006) Hypoxia, red blood cells, and nitrite regulate NO–dependent hypoxic vasodilation, Blood, 107, 566–574.Google Scholar
  35. 35.
    Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., Huang, K. T., Shields, H., Kim–Shapiro, D. B., Schechte, A. N., Cannon, R. O., 3rd, and Gladwin, M. T. (2003) Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation, Nat. Med., 9, 1498–1505.CrossRefPubMedGoogle Scholar
  36. 36.
    Rifkind, J. M., Nagababu, E., Barbiro–Michaely, E., Ramasamy, S., Pluta, R. M., and Mayevsky, A. (2007) Nitrite infusion increases cerebral blood flow and decreases mean arterial blood pressure in rats: a role for red cell NO, Nitric Oxide, 16, 448–456.CrossRefPubMedGoogle Scholar
  37. 37.
    Richards, J. C., Racine, M. L., Hearon, C. M., Jr., Kunkel, M., Luckasen, G. J., Larson, D. G., Allen, J. D., and Dinenno, F. A. (2018) Acute ingestion of dietary nitrate increases muscle blood flow via local vasodilation during handgrip exercise in young adults, Physiol. Rep., 6, e13572.CrossRefPubMedCentralGoogle Scholar
  38. 38.
    Cao, Z., Bell, J. B., Mohanty, J. G., Nagababu, E., and Rifkind, J. M. (2009) Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite–induced vasodilation, Am. J. Physiol. Heart. Circ. Physiol., 297, 1494–1503.CrossRefGoogle Scholar
  39. 39.
    Irzhak, L. I. (1975) Hemoglobins and Their Properties [in Russian], Nauka, Moscow.Google Scholar
  40. 40.
    Tyuma, I. (1984) The Bohr effect and the Haldane effect in human hemoglobin, Jpn. J. Physiol., 34, 205–216.CrossRefPubMedGoogle Scholar
  41. 41.
    Jensen, F. B. (2004) Red blood cell pH, the Bohr effect, and other oxygenation–linked phenomena in blood O2 and CO2 transport, Acta Physiol. Scand., 182, 215–227.PubMedGoogle Scholar
  42. 42.
    Perutz, M. F. (1970) Stereochemistry of cooperative effects in haemoglobin: haem–haem interaction and the problem of allostery, Nature, 228, 726–734.CrossRefPubMedGoogle Scholar
  43. 43.
    Kamshilov, I. M., and Zaprudnova, R. A. (2013) The Bohr effect in the feature of buffer properties of fish hemoglobin, Trudy Karel. Nauch. Tsentra RAN, No. 3, 190–193.Google Scholar
  44. 44.
    Sakai, Y., Miwa, M., Oe, K., Ueha, T., Koh, A., Niikura, T., Iwakura, T., Lee, S. Y., Tanaka, M., and Kurosaka, M. (2011) A novel system for transcutaneous application of carbon dioxide causing an “artificial Bohr effect” in the human body, PLoS One, 6, e24137.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Giardina, B., Messana, I., Scatena, R., and Castagnola, M. (1995) The multiple functions of haemoglobin, Crit. Rev. Biochem. Mol. Biol., 30, 165–196.CrossRefPubMedGoogle Scholar
  46. 46.
    Anderson, H. M., and Turner, J. C. (1959) Preparation and the haemoglobin content of red cell “ghosts”, Nature, 183, 112–113.CrossRefPubMedGoogle Scholar
  47. 47.
    Anderson, H. M., and Turner, J. C. (1960) Relation of hemoglobin to the red cell membrane, J. Clin. Invest., 39, 1–7.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Gromov, P. S., Zakharov, S. F., Shishkin, S. S., and Il’inskiy, R. V. (1988) 2D map of human erythrocyte membrane proteins, Biokhimiya, 53, 1316–1326.Google Scholar
  49. 49.
    Toktamysova, Z. S., and Birzhanova, N. Kh. (1990) Regarding a membrane–bound hemoglobin, Biofizika, 35, 1019–1020.PubMedGoogle Scholar
  50. 50.
    Chu, H., and Low, P. S. (2006) Mapping of glycolytic enzyme–binding sites on human erythrocyte band 3, Biochem. J., 400, 143–151.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Pivovarov, Yu. I., Kuznetsova, E. E., Gorokhova, V. G., Sergeeva, A. S., Babushkina, I. V., Koryakina, L. B., and Andreeva, E. O. (2016) Level of membrane–bound hemoglobin and erythrocyte membrane proteins in patients with hypertensive disease complicated and uncomplicated with metabolic syndrome, Byull. Vost.–Sib. Nauch. Tsentra Sib. Otdel. Ros. Akad. Med. Nauk, No. 1, 61–67.Google Scholar
  52. 52.
    Chuyko, E. S., Orlova, G. M., Kuznetsova, E. E., and Gorokhova, V. G. (2015) Membrane–bound erythrocyte hemoglobin and methemoglobin in patients with ischemic heart disease, ENI Zabaykal. Med. Vest., No. 3, 9–12.Google Scholar
  53. 53.
    Sozarukova, M. M., Vladimirov, G. K., and Izmaylov, D. Yu. (2015) Membrane–bound erythrocyte hemoglobin as a potential source of free radicals, in Materials of the Sci. Conf. “Science and Practice: New Discoveries”, Karlovy Vary–Moscow, October 24–25, 2015, International Center of Research Projects, Kirov, pp. 771–780.Google Scholar
  54. 54.
    Nasybullina, E. I., Kosmachevskaya, O. V., and Topunov, A. F. (2018) Effect of metabolites nitric oxide on generation of membrane–bound hemoglobin in carbonyl stress, Trudy Karel. Nauch. Tsentra RAN, No. 4, 93–104.Google Scholar
  55. 55.
    De Rosa, M. C., Alinovi, C. C., Galtieri, A., Scatena, R., and Giardina, B. (2007) The plasma membrane of erythrocytes plays a fundamental role in the transport of oxygen, carbon dioxide and nitric oxide and in the maintenance of the reduced state of the heme iron, Gene, 398, 162–171.PubMedGoogle Scholar
  56. 56.
    Shaklai, N., Yguerabide, J., and Ranney, H. M. (1977) Classification and localization of hemoglobin binding sites on the red blood cell membrane, Biochemistry, 16, 5593–5597.CrossRefPubMedGoogle Scholar
  57. 57.
    Sega, M. F., Chu, H., Christian, J., and Low, P. S. (2012) Interaction of deoxyhemoglobin with the cytoplasmic domain of murine erythrocyte band 3, Biochemistry, 51, 3264–3272.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Walder, J. A., Chatterjee, R., Steck, T. L., Low, P. S., Musso, G. F., Kaiser, E. T., Rogers, P. H., and Arnone, A. (1984) The interaction of hemoglobin with the cytoplasmic domain of band 3 of the human erythrocyte membrane, J. Biol. Chem., 259, 10238–10246.PubMedGoogle Scholar
  59. 59.
    Shaklai, N., Sharma, V. S., and Ranney, H. M. (1981) Interaction of sickle cell hemoglobin with erythrocyte membranes, Proc. Natl. Acad. Sci. USA, 78, 65–68.CrossRefPubMedGoogle Scholar
  60. 60.
    Demehin, A. A., Abugo, O. O., Jayakumar, J. R., and Rifkind, J. M. (2002) Binding of hemoglobin to red cell membranes with eosin–5–maleimide–labeled band 3: analysis of centrifugation and fluorescence data, Biochemistry, 41, 8630–8637.CrossRefPubMedGoogle Scholar
  61. 61.
    Chan, E., and Desforges, J. F. (1976) The role of disulfide bonds in Heinz body attachment to membranes, Br. J. Haematol., 33, 371–378.CrossRefPubMedGoogle Scholar
  62. 62.
    Sharma, R., and Premachandra, B. R. (1991) Membrane–bound hemoglobin as a marker of oxidative injury in adult and neonatal red blood cells, Biochem. Med. Metab. Biol., 46, 33–44.CrossRefPubMedGoogle Scholar
  63. 63.
    Datta, P., Chakrabarty, S., Chakrabarty, A., and Chakrabarty, A. (2008) Membrane interactions of hemoglobin variants, HbA, HbE, HbF and globin subunits of HbA: effects of aminophospholipids and cholesterol, Biochim. Biophys. Acta, 1778, 1–9.Google Scholar
  64. 64.
    Giardina, B., Scatena, R., Clementi, M. E., Ramacci, M. T., Maccari, F., Cerroni, L., and Condo, S. G. (1991) Selective binding of met–hemoglobin to erythrocytic membrane: a possible involvement in red blood cell aging, Adv. Exp. Med. Biol., 307, 75–84.CrossRefPubMedGoogle Scholar
  65. 65.
    Topunov, A. F., and Golubeva, L. I. (1989) Reductases reducing oxygen–carrying hemoproteins: hemoglobin, myoglobin and leghemoglobin, Usp. Biol. Khim., 30, 239–252.Google Scholar
  66. 66.
    Shaklai, N., and Ranney, H. R. (1978) Interaction of hemoglobin with membrane lipids: a source of pathological phenomena, Isr. J. Med. Sci., 14, 1152–1156.PubMedGoogle Scholar
  67. 67.
    Kumar, S., and Bandyopadhyay, U. (2005) Free heme toxicity and its detoxification systems in human, Toxicol. Lett., 157, 175–188.CrossRefPubMedGoogle Scholar
  68. 68.
    Kriebardis, A. G., Antonelou, M. H., Stamoulis, K. E., Economou–Petersen, E., Margaritis, L. H., and Papassideri, I. S. (2007) Progressive oxidation of cytoskeletal proteins and accumulation of denatured hemoglobin in stored red cells, J. Cell. Mol. Med., 11, 148–155.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Luckey, M. (2008) Membrane Structural Biology with Biochemical and Biophysical Foundations, Cambridge University Press, Cambridge, N. Y., USA.CrossRefGoogle Scholar
  70. 70.
    Tsuneshige, A., Imai, K., and Tyuma, I. (1987) The binding of hemoglobin to red cell membrane lowers its oxygen affinity, J. Biochem., 101, 695–704.CrossRefPubMedGoogle Scholar
  71. 71.
    Korobov, V. M. (1999) Effect of carnosine on the erythrocyte membrane in normal states and in diabetes, Ukr. Biokhim. Zh., 72, 94–96.Google Scholar
  72. 72.
    Salhany, J. M. (2008) Kinetics of reaction of nitrite with deoxy hemoglobin after rapid deoxygenation or predeoxy–genation by dithionite measured in solution and bound to the cytoplasmic domain of band 3 (SLC4A1), Biochemistry, 47, 6059–6072.CrossRefPubMedGoogle Scholar
  73. 73.
    Chu, H., Breite, A., Ciraolo, P., Franco, R. S., and Low, P. S. (2008) Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: implications for O2 regulation of erythrocyte properties, Blood, 111, 932–938.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Puchulu–Campanella, E., Chu, H., Anstee, D. J., Galan, J. A., Tao, W. A., and Low, P. S. (2013) Identification of the components of a glycolytic enzyme metabolon on the human red blood cell membrane, J. Biol. Chem., 288, 848–858.CrossRefPubMedGoogle Scholar
  75. 75.
    Messana, I., Orlando, M., Cassiano, L., Pennacchietti, L., Zuppi, C., Castagnola, M., and Giardina, B. (1996) Human erythrocyte metabolism is modulated by the O2–linked transition of hemoglobin, FEBS Lett., 390, 25–28.CrossRefPubMedGoogle Scholar
  76. 76.
    Weber, R. E., Voelter, W., Fago, A., Echner, H., Campanella, E., and Low, P. S. (2004) Modulation of red cell glycolysis: interactions between vertebrate hemoglobins and cytoplasmic domains of band 3 red cell membrane proteins, Am. J. Physiol. Regul. Integr. Comp. Physiol., 287, 454–464.CrossRefGoogle Scholar
  77. 77.
    Sprague, R. S., Stephenson, A. H., and Ellsworth, M. L. (2007) Red not dead: signaling in and from erythrocytes, Trends Endocrin. Metab., 18, 350–355.CrossRefGoogle Scholar
  78. 78.
    Ellsworth, M. L., Ellis, C. G., Goldman, D., Stephenson, A. H., Dietrich, H. H., and Sprague, R. S. (2009) Erythrocytes: oxygen sensors and modulators of vascular tone, Physiology (Bethesda), 24, 107–116.Google Scholar
  79. 79.
    Ramdani, G., and Langsley, G. (2014) ATP, an extracellular signaling molecule in red blood cells: a messenger for malaria? Biomed. J., 37, 284–292.CrossRefPubMedGoogle Scholar
  80. 80.
    Thevenin, B. J.–M., Willardson, B. M., and Low, P. S. (1989) The redox state of cysteines 201 and 317 of the erythrocyte anion exchanger is critical for ankyrin binding, J. Biol. Chem., 264, 15886–15892.PubMedGoogle Scholar
  81. 81.
    Soszynski, M., and Bartosz, G. (1997) Penetration of erythrocyte membrane by peroxynitrite: participation of the anion exchange protein, Biochem. Mol. Biol. Int., 43, 319–325.PubMedGoogle Scholar
  82. 82.
    Shingles, R., Roh, M. H., and McCarty, R. E. (1997) Direct measurement of nitrite transport across erythrocyte membrane vesicles using the fluorescent probe, 6–methoxy–N–(3–sulfopropyl) quinolinium, J. Bioenerg. Biomembr., 29, 611–616.CrossRefPubMedGoogle Scholar
  83. 83.
    Matsumoto, A., and Gow, A. J. (2011) Membrane transfer of S–nitrosothiols, Nitric Oxide, 25, 102–107.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Huang, Z., Louderback, J. G., Goyal, M., Azizi, F., King, S. B., and Kim–Shapiro, D. B. (2001) Nitric oxide binding to oxygenated hemoglobin under physiological conditions, Biochim. Biophys. Acta, 1568, 252–560.CrossRefPubMedGoogle Scholar
  85. 85.
    Kuhn, V., Diederich, L., Keller, T. C. S., IV, Kramer, C. M., Luckstadt, W., Panknin, C., Suvorava, T., Isakson, B. E., Kelm, M., and Cortese–Krott, M. M. (2017) Red blood function and dysfunction: redox regulation, nitric oxide metabolism, anemia, Antioxid. Redox Signal., 26, 718–742.CrossRefGoogle Scholar
  86. 86.
    Vaughn, M. W., Huang, K.–T., Kuo, L., and Liao, J. C. (2000) Erythrocytes possess an intrinsic barrier to nitric oxide consumption, J. Biol. Chem., 275, 2342–234.CrossRefPubMedGoogle Scholar
  87. 87.
    Han, T. H., Hyduke, D. R., Vaughn, M. W., Fukuto, J. M., and Liao, J. C. (2002) Nitric oxide reaction with red blood cells and hemoglobin under heterogeneous conditions, Proc. Natl. Acad. Sci. USA, 99, 7763–7768.CrossRefPubMedGoogle Scholar
  88. 88.
    Gladwin, M. T., Crawford, J. H., and Patel, R. P. (2004) The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation, Free Radic. Biol. Med., 36, 707–717.PubMedGoogle Scholar
  89. 89.
    Bergfeld, G. R., and Forrester, T. (1992) Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia, Cardiovasc. Res., 26, 40–47.CrossRefPubMedGoogle Scholar
  90. 90.
    Jagger, J. E., Bateman, R. M., Ellsworth, M. L., and Ellis, C. G. (2001) Role of erythrocyte in regulating local O2 delivery mediated by hemoglobin oxygenation, Am. J. Physiol. Heart. Circ. Physiol., 280, 2833–2839.CrossRefGoogle Scholar
  91. 91.
    Sprague, R. S., Ellsworth, M. L., Stephenson, A. H., and Lonigro, A. J. (2001) Participation of cAMP in a signal–transduction pathway relating erythrocyte deformation to ATP release, Am. J. Physiol. Cell. Physiol., 281, 1158–1164.CrossRefGoogle Scholar
  92. 92.
    Olearczyk, J. J., Stephenson, A. H., Lonigro, A. J., and Sprague, R. S. (2004) Heterotrimeric, G protein Gi is involved in a signal transduction pathway for ATP release from erythrocytes, Am. J. Physiol. Heart. Circ. Physiol., 286, 940–945.Google Scholar
  93. 93.
    Luneva, O. G., Sidorenko, S. V., Maksimov, G. V., Grigorchik, R., and Orlov, S. N. (2015) Erythrocytes as vascular tone regulators, Biol. Membr. (Moscow), 32, 223–234.Google Scholar
  94. 94.
    Stefanovic, M., Puchulu–Campanella, E., Kodippili, G., and Low, P. S. (2013) Oxygen regulates the band 3–ankyrin bridge in the human erythrocyte membrane, Biochem. J., 449, 143–150.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Ito, H., Murakami, R., Sakuma, S., Tsai, C. D., Gutsmann, T., Brandenburg, K., Poschl, J. M., Arai, F., Kaneko, M., and Tanaka, M. (2017) Mechanical diagnosis of human erythrocytes by ultra–high speed manipulation unraveled critical time window for global cytoskeletal remodeling, Sci. Rep., 7, 43134.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Sikora, J., Orlov, S. N., Furuya, K., and Grygorczyk, R. (2014) Hemolysis is a primary ATP–release mechanism in human erythrocytes, Blood, 124, 2150–2157.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Luneva, O. G., Sidorenko, S. V., Ponomarchuk, O. O., Tverskoy, A. M., Cherkashin, A. A., Rodnenkov, O. V., Alekseeva, N. V., Deev, L. I., Maksimov, G. V., Grygorczyk, R., and Orlov, S. N. (2016) Deoxygenation affects composition of membrane–bound proteins in human erythrocytes, Cell Physiol. Biochem., 39, 81–88.CrossRefPubMedGoogle Scholar
  98. 98.
    Grygorczyk, R., and Orlov, S. N. (2017) Effects of hypoxia on erythrocyte membrane properties–implications for intravascular hemolysis and purinergic control of blood flow, Front. Physiol., 8, 1110.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    O’Neill, J. S., and Reddy, A. B. (2011) Circadian clocks in human red blood cells, Nature, 469, 498–503.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Cho, C. S., Yoon, H. J., Kim, J. Y., Woo, H. A., and Rhee, S. G. (2014) Circadian rhythm of hyperoxidized peroxire–doxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells, Proc. Natl. Acad. Sci. USA, 111, 12043–12048.CrossRefPubMedGoogle Scholar
  101. 101.
    Latenkov, V. P. (1986) Circadian rhythm in blood acid–base balance and gas composition, Byull. Eksp. Biol. Med., 101, 614–616.CrossRefGoogle Scholar
  102. 102.
    Klei, T. R., Meinderts, S. M., van den Berg, T. K., and van Bruggen, R. (2017) From the cradle to the grave: the role of macrophages in erythropoiesis and erythrophagocytosis, Front. Immunol., 8,73.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Badior, K. E., and Casey, J. R. (2018) Molecular mechanism for the red blood cell senescence clock, IUBMB Life, 70, 32–40.CrossRefPubMedGoogle Scholar
  104. 104.
    Waugh, S. M., and Low, P. S. (1985) Hemichrome binding to band 3: nucleation of Heinz bodies on the erythrocyte membrane, Biochemistry, 24, 34–39.CrossRefPubMedGoogle Scholar
  105. 105.
    McPherson, R. A., Sawyer, W. H., and Tilley, L. (1992) Rotational diffusion of the erythrocyte integral membrane protein band 3: effect of hemichrome binding, Biochemistry, 31, 512–518.CrossRefPubMedGoogle Scholar
  106. 106.
    Bosman, G. J. (2016) The proteome of the red blood cell: an auspicious source of new insights into membrane–centered regulation of homeostasis, Proteomes, 4, E35.CrossRefPubMedGoogle Scholar
  107. 107.
    Arashiki, N., Kimata, N., Manno, S., Mohandas, N., and Takakuwa, Y. (2013) Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence, Biochemistry, 52, 5760–5769.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Briglia, M., Rossi, M. A., and Faggio, C. (2017) Eryptosis: ally or enemy, Curr. Med. Chem., 24, 937–942.CrossRefGoogle Scholar
  109. 109.
    Pantaleo, A., Ferru, E., Pau, M. C., Khadjavi, A., Mandili, G., Matte, A., Spano, A., De Franceschi, L., Pippia, P., and Turrini, F. (2016) Band 3 erythrocyte membrane protein acts as redox stress sensor leading to its phos-phorylation by p72Syk, Oxid. Med. Cell. Longev., 2016, 6051093.CrossRefPubMedGoogle Scholar
  110. 110.
    Ferru, E., Pantaleo, A., Carta, F., Mannu, F., Khadjavi, A., Gallo, V., Ronzoni, L., Graziadei, G., Cappellini, M. D., and Turrini, F. (2014) Thalassemic erythrocytes release microparticles loaded with hemichromes by redox activation of p72Syk kinase, Haematologica, 99, 570–578.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Ferru, E., Giger, K., Pantaleo, A., Campanella, E., Grey, J., Ritchie, K., Vono, R., Turrini, F., and Low, P. S. (2011) Regulation of membrane–cytoskeletal interactions by tyrosine phosphorylation of erythrocyte band 3, Blood, 117, 5998–6006.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Golubchikov, O. A., and Berezin, B. D. (1986) Applies aspects of porphyrins, Usp. Khim., 55, 361–1389.CrossRefGoogle Scholar
  113. 113.
    Maples, K. R., Eyer, P., and Mason, R. P. (1990) Aniline–, phenylhydroxylamine–, nitrosobenzene–, and nitroben–zene–induced hemoglobin thiyl free radical formation in vivo and in vitro, Mol. Pharmacol., 37, 311–318.PubMedGoogle Scholar
  114. 114.
    Jia, Y., Buehler, P. W., Boykins, R. A., Venable, R. M., and Alayash, A. I. (2007) Structural basis of peroxide–mediated changes in human hemoglobin: a novel oxidative path-way, J. Biol. Chem., 282, 4894–4907.CrossRefPubMedGoogle Scholar
  115. 115.
    Vallelian, F., Pimenova, T., Pereira, C. P., Abraham, B., Mikolajczyk, M. G., Schoedon, G., Schoedon, G., Zenobi, R., Alayash, A. I., Buehler, P. W., and Schaer, D. J. (2008) The reaction of hydrogen peroxide with hemoglobin induces extensive alpha–globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways, Free Radic. Biol. Med., 45, 1150–1158.CrossRefPubMedGoogle Scholar
  116. 116.
    Umbreit, J. (2007) Methemoglobin–it’s not just blue: a concise review, Am. J. Hematol., 82, 134–144.CrossRefPubMedGoogle Scholar
  117. 117.
    Silkstone, G. G., Silkstone, R. S., Wilson, M. T., Simons, M., Bulow, L., Kallberg, K., Ratanasopa, K., Ronda, L., Mozzarelli, A., Reeder, B. J., and Cooper, C. E. (2016) Engineering tyrosine electron transfer pathways decreases oxidative toxicity in hemoglobin: implications for blood substitute design, Biochem. J., 473, 3371–3383.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Widmer, C. C., Pereira, C. P., Gehrig, P., Vallelian, F., Schoedon, G., Buehler, P. W., and Schaer, D. J. (2010) Hemoglobin can attenuate hydrogen peroxide–induced oxidative stress by acting as an antioxidative peroxidase, Antioxid. Redox Signal., 12, 185–198.CrossRefPubMedGoogle Scholar
  119. 119.
    Grigorieva, D. V., Gorudko, I. V., Sokolov, A. V., Kosmachevskaya, O. V., Topunov, A. F., Buko, I. V., Konstantinova, E. E., Cherenkevich, S. N., and Panasenko, O. N. (2013) Measurement of plasma hemo–globin peroxidase activity, Bull. Exp. Biol. Med., 155, 118–121.CrossRefPubMedGoogle Scholar
  120. 120.
    Huang, L., Wojciechowski, G., and Ortiz de Montellano, P. R. (2006) Role of heme–protein covalent bonds in mammalian peroxidases: protection of the heme by a single engineered hemeprotein link in horseradish peroxidase, J. Biol. Chem., 281, 18983–18938.CrossRefPubMedGoogle Scholar
  121. 121.
    Grutzner, A., Garcia–Manyes, S., Kotter, S., Badilla, C. L., Fernandez, J. M., and Linke, W. A. (2009) Modulation of titin–based stiffness by disulfide bonding in the cardiac titin N2–B unique sequence, Biophys. J., 97, 825–834.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Golly, I., and Hlavica, P. (1983) The role of hemoglobin in the N–oxidation of 4–chloroaniline, Biochim. Biophys. Acta, 760, 69–76.CrossRefPubMedGoogle Scholar
  123. 123.
    Miyazaki, K., Arai, S., Iwamoto, T., Takasaki, M., and Tomoda, A. (2004) Metabolism of pyrogallol to purpuro–gallin by human erythrocytic hemoglobin, Tohoku J. Exp. Med., 203, 319–330.CrossRefPubMedGoogle Scholar
  124. 124.
    George, P., and Irvine, D. H. (1951) Reaction of metmyo–globin with hydrogen peroxide, Nature, 168, 164–165.CrossRefPubMedGoogle Scholar
  125. 125.
    Schaer, D. J., Buehler, P. W., Alayash, A. I., Belcher, J. D., and Vercellotti, G. M. (2013) Hemolysis and free hemo–globin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins, Blood, 121, 1276–1284.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Nagakubo, T., Kumano, T., Hashimoto, Y., and Kobayashi, M. (2018) Hemoglobin catalyzes CoA degra–dation and thiol addition to flavonoids, Sci. Rep., 8, 1282.CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Elbaum, D., and Nagel, R. L. (1981) Esterase activity of hemoglobin. Differences between HB A and HB S, J. Biol. Chem., 256, 2280–2283.PubMedGoogle Scholar
  128. 128.
    Kuhn, H., Gotze, R., Schewe, T., and Rapoport, S. M. (1981) Quasi–lipoxygenase activity of haemoglobin. A model for lipoxygenases, Eur. J. Biochem., 120, 161–168.CrossRefPubMedGoogle Scholar
  129. 129.
    Rother, R. P., Bell, L., Hillmen, P., and Gladwin, M. T. (2005) The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease, JAMA, 293, 1653–1662.CrossRefPubMedGoogle Scholar
  130. 130.
    Schaer, C. A., Deuel, J. W., Bittermann, A. G., Rubio, I. G., Schoedon, G., Spahn, D. R., Wepf, R. A., Vallelian, F., and Schaer, D. J. (2013) Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage, Cell Death Differ., 20, 1569–1579.CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Reiter, C. D., Wang, X., Tanus–Santos, J. E., Hogg, N., Cannon, R. O., Schechter, A. N., and Gladwin, M. T. (2002) Cell–free hemoglobin limits nitric oxide bioavailability in sickle–cell disease, Nat. Med., 8, 1383–1289.CrossRefPubMedGoogle Scholar
  132. 132.
    Grinshtein, N., Bamm, V. V., Tsemakhovich, V. A., and Shaklai, N. (2003) Mechanism of low–density lipoprotein oxidation by hemoglobin–derived iron, Biochemistry, 42, 6977–6985.CrossRefPubMedGoogle Scholar
  133. 133.
    Cooper, C. E., Schaer, D. J., Buehler, P. W., Wilson, M. T., Reeder, B. J., Silkstone, G., Svistunenko, D. A., Bulow, L., and Alayash, A. I. (2012) Haptoglobin binding stabilizes hemoglobin ferryl iron and the globin radical on tyrosine beta145, Antioxid. Redox Signal., 18, 2264–2273.CrossRefPubMedGoogle Scholar
  134. 134.
    Kapralov, A., Vlasova, I. I., Feng, W., Maeda, A., Walson, K., Tyurin, V. A., Huang, Z., Aneja, R. K., Carcillo, J., Bayr, H., and Kagan, V. E. (2009) Peroxidase activity of hemoglobin·haptoglobin complexes. Covalent aggregation and oxidative stress in plasma and macrophages, J. Biol. Chem., 284, 30395–30407.CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Choi, A. M., and Alam, J. (1996) Heme oxygenase–1: function, regulation, and implication of a novel stress–inducible protein in oxidant–induced lung injury, J. Respir. Cell Mol. Biol., 15, 9–19.Google Scholar
  136. 136.
    Bianchetti, C. M., Yi, L., Ragsdale, S. W., and Philips, G. N., Jr. (2007) Comparison of apo–and heme–bound crystal structures of a truncated human heme oxygenase–2, J. Biol. Chem., 282, 37624–37631.CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Ryter, S. W., and Tyrrell, R. M. (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity: heme oxygenase has both pro–and antioxidant properties, Free Radic. Biol. Med., 28, 289–309.CrossRefPubMedGoogle Scholar
  138. 138.
    Wagener, F. A., Volk, H. D., Willis, D., Abraham, N. G., Soares, M. P., Adema, G. J., and Figdor, C. G. (2003) Different faces of the heme–heme oxygenase system in inflammation, Pharmacol. Rev., 55, 551–571.CrossRefPubMedGoogle Scholar
  139. 139.
    Shimizu, T., Huang, D., Yan, F., Stranava, M., Bartosova, M., Fojtikova, V., and Martinkova, M. (2015) Gaseous O2, NO, and CO in signal transduction: structure and function relationships of heme–based gas sensors and heme–redox sensors, Chem. Rev., 115, 6491–6533.Google Scholar
  140. 140.
    Stec, D. E., Drummond, H. A., and Vera, T. (2008) Role of carbon monoxide in blood pressure regulation, Hypertension, 51, 597–604.CrossRefPubMedGoogle Scholar
  141. 141.
    Stocker, R., Yamamoto, Y., McDonagh, A. F., Glazer, A. N., and Ames, B. N. (1987) Bilirubin is an antioxidant of possible physiological importance, Science, 235, 1043–1046.CrossRefPubMedGoogle Scholar
  142. 142.
    Baranano, D. E., Rao, M., Ferris, C. D., and Snyder, S. H. (2002) Biliverdin reductase: a major physiologic cytopro–tectant, Proc. Natl. Acad. Sci. USA, 99, 16093–16098.CrossRefPubMedGoogle Scholar
  143. 143.
    Fondevila, C., Shen, X. D., Tsuchiyashi, S., Yamashita, K., Csizmadia, E., Lassman, C., Busuttil, R. W., Kupiec–Weglinski, J. W., and Bach, F. H. (2004) Biliverdin therapy protects rat livers from ischemia and reperfusion injury, Hepatology, 40, 1333–1341.CrossRefPubMedGoogle Scholar
  144. 144.
    Spetzler, V., Goldaracena, N., Kaths, J. M., Marquez, M., Selzner, M., and Selzner, N. (2017) Elevated preoperative serum bilirubin improves reperfusion injury and survival postliver transplantation, Transplant Direct., 3, e187.CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Li, J. J., Zou, Z. Y., Liu, J., Xiong, L. L., Jiang, H. Y., Wang, T. H., and Shao, J. L. (2017) Biliverdin administration ameliorates cerebral ischemia reperfusion injury in rats and is associated with proinflammatory factor down–regulation, Exp. Ther. Med., 14, 671–679.CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Potor, L., Nagy, P., Mehes, G., Hendrik, Z., Jeney, V., Petho, D., Vasas, A., Palinkas, Z., Balogh, E., Gyetvai, A., Whiteman, M., Torregrossa, R., Wood, M. E., Olvaszto, S., Nagy, P., Balla, G., and Balla, J. (2018) Hydrogen sulfide abrogates hemoglobin–lipid interaction in atherosclerotic lesion, Oxid. Med. Cell. Longev., 2018, 3812568.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Korovila, I., Hugo, M., Castro, J. P., Weber, D., Hohn, A., Grune, T., and Jung, T. (2017) Proteostasis, oxidative stress and aging, Redox Biol., 13, 550–567.Google Scholar
  148. 148.
    Otterbein, L. E., Soares, M. P., Yamashita, K., and Bach, F. H. (2003) Heme oxygenase–1: unleashing the protective properties of heme, Trends Immunol., 24, 449–455.CrossRefPubMedGoogle Scholar
  149. 149.
    Konrad, F. M., Zwergel, C., Ngamsri, K. C., and Reutershan, J. (2017) Anti–inflammatory effects of heme oxygenase–1 depend on adenosine A2A–and A2B–receptor signaling in acute pulmonary inflammation, Front. Immunol., 8, 1874.CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Guarda, C. C. D., Santiago, R. P., Fiuza, L. M., Aleluia, M. M., Ferreira, J. R. D., Figueiredo, C. V. B., Yahouedehou, S. C. M. A., Oliveira, R. M., Lyra, I. M., and Goncalves, M. S. (2017) Heme–mediated cell activation: the inflammatory puzzle of sickle cell anemia, Expert. Rev. Hematol., 10, 533–541.CrossRefPubMedGoogle Scholar
  151. 151.
    Righy, C., Turon, R., Freitas, G., Japiassu, A. M., Faria Neto, H. C. C., Bozza, M., Oliveira, M. F., and Bozza, F. A. (2018) Hemoglobin metabolism by–products are associated with an inflammatory response in patients with hemorrhagic stroke, Rev. Bras. Ter. Intensiva., 30, 21–27.CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Merle, N. S., Grunenwald, A., Figueres, M. L., Chauvet, S., Daugan, M., Knockaert, S., Robe–Rybkine, T., Noe, R., May, O., Frimat, M., Brinkman, N., Gentinetta, T., Miescher, S., Houillier, P., Legros, V., Gonnet, F., Blanc–Brude, O. P., Rabant, M., Daniel, R., Dimitrov, J. D., and Roumenina, L. T. (2018) Characterization of renal injury and inflammation in an experimental model of intravascular hemolysis, Front. Immunol., 9,179.CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Dutra, F. F., and Bozza, M. T. (2014) Heme on innate immunity and inflammation, Front. Pharmacol., 5,115.CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Shayeghi, M., Latunde–Dada, G. O., Oakhill, J. S., Laftah, A. H., Takeuchi, K., Halliday, N., Khan, Y., Warley, A., McCann, F. E., Hider, R. C., Frazer, D. M., Anderson, G. J., Vulpe, C. D., Simpson, R. J., and McKie, A. T. (2005) Identification of an intestinal heme transporter, Cell, 122, 789–801.CrossRefPubMedGoogle Scholar
  155. 155.
    Figueiredo, R. T., Fernandez, P. L., Mourao–Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., Oliveira, M. F., Oliveira, P. L., Graca–Souza, A. V., and Bozza, M. T. (2007) Characterization of heme as activator of Toll–like receptor, J. Biol. Chem., 282, 20221–20229.CrossRefPubMedGoogle Scholar
  156. 156.
    Lin, T., Kwak, Y. H., Sammy, F., He, P., Thundivalappil, S., Su, G., Chao, W., and Shaw, H. (2010) Warren synergistic inflammation is induced by blood degradation products with microbial Toll–like receptor agonists and is blocked by hemopexin, J. Infect. Dis., 202, 624–632.CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Belcher, J. D., Chen, C., Nguyen, J., Milbauer, L., Abdulla, F., Alayash, A. I., Smith, A., Nath, K. A., Hebbel, R. P., and Vercellotti, G. M. (2014) Heme triggers TLR4 signaling leading to endothelial cell activation and vaso–occlusion in murine sickle cell disease, Blood, 123, 377–390.CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Horrigan, F. T., Heinemann, S. H., and Hoshi, T. (2005) Heme regulates allosteric activation of the Slo1 BK channel, J. Gen. Physiol., 126, 7–21.CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Mil’to, I. V., Sukhodolo, I. V., Prokop’eva, V. D., and Kliment’eva, T. K. (2016) Molecular and cellular basics of iron metabolism in human, Biokhimiya, 81, 725–742.Google Scholar
  160. 160.
    Lang, E., Bissinger, R., Qadri, S. M., and Lang, F. (2017) Suicidal death of erythrocytes in cancer and its chemotherapy: a potential target in the treatment of tumor–associated anemia, Int. J. Cancer, 141, 1522–1528.CrossRefPubMedGoogle Scholar
  161. 161.
    Kriventsev, Yu. A., and Nikulina, D. M. (2018) Biochemistry: Structure and Role of Hemoglobin Profile Proteins [in Russian], Yurait, Moscow.Google Scholar
  162. 162.
    Lane, N. (2002) Oxygen: The Molecule that Made the World, Oxford University Press, Oxford, UK.Google Scholar
  163. 163.
    Brantl, V., Gramsch, C., Lottspeich, F., Mertz, R., Jaeger, K. H., and Herz, A. (1986) Novel opioid peptides derived from hemoglobin: hemorphins, Eur. J. Pharmacol., 125, 309–310.CrossRefPubMedGoogle Scholar
  164. 164.
    Gomes, I., Dale, C. S., Casten, K., Geigner, M. A., Gozzo, F. C., Ferro, E. S., Heimann, A. S., and Devi, L. A. (2010) Hemoglobin–derived peptides as novel type of bioactive signaling molecules, AAPS J., 12, 658–669.CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Heimann, A. S., Gomes, I., Dale, C. S., Pagano, R. L., Gupta, A., de Souza, L. L., Luchessi, A. D., Castro, L. M., Giorgi, R., Rioli, V., Ferro, E. S., and Devi, L. A. (2007) Hemopressin is an inverse agonist of CB1 cannabinoid receptors, Proc. Natl. Acad. Sci. USA, 104, 20588–20593.CrossRefPubMedGoogle Scholar
  166. 166.
    Nyberg, F., Sanderson, K., and Glamsta, E. L. (1997) The hemorphins: a new class of opioid peptides derived from the blood protein hemoglobin, Biopolymers, 43, 147–516.CrossRefPubMedGoogle Scholar
  167. 167.
    Moeller, I., Albiston, A. L., Lew, R. A., Mendelsohn, F. A., and Chai, S. Y. (1999) A globin fragment, LVV–hemorphin–7, induces [3H]thymidine incorporation in a neuronal cell line via the AT4 receptor, J. Neurochem., 73, 301–308.Google Scholar
  168. 168.
    Cejka, J., Zelezna, B., Velek, J., Zicha, J., and Kunes, J. (2004) LVV–hemorphin–7 lowers blood pressure in spontaneously hypertensive rats: radiotelemetry study, Physiol. Res., 53, 603–607.PubMedGoogle Scholar
  169. 169.
    Fruitier–Arnaudin, I., Cohen, M., Bordenave, S., Sannier, F., and Piot, J. M. (2002) Comparative effects of angiotensin IV and two hemorphins on angiotensin–converting enzyme activity, Peptides, 23, 1465–1470.CrossRefPubMedGoogle Scholar
  170. 170.
    Collinder, E., Nyberg, F., Sanderson–Nydahl, K., Gottlieb–Vedi, M., and Lindholm, A. (2005) The opioid haemorphin–7 in horses during low–speed and high–speed treadmill exercise to fatigue, J. Vet. Med. A. Physiol. Pathol. Clin. Med., 52, 162–165.CrossRefPubMedGoogle Scholar
  171. 171.
    Lee, J., Albiston, A. L., Allen, A. M., Mendelsohn, F. A., Ping, S. E., Barrett, G. L., Murphy, M., Morris, M. J., McDowall, S. G., and Chai, S. Y. (2004) Effect of I. C. V. injection of AT4 receptor ligands, NLE1–angiotensin IV and LVV–hemorphin 7, on spatial learning in rats, Neuroscience, 124, 341–349.PubMedGoogle Scholar
  172. 172.
    Shamova, E. V., Bichan, O. D., Drozd, E. S., Gorudko, I. V., Chizhik, S. A., Shumaev, K. B., Cherenkevich, S. N., and Vanin, A. F. (2011) Regulation of platelet and erythrocyte functional and mechanical properties by donors of nitric oxide, Biofizika, 56, 265–271.PubMedGoogle Scholar
  173. 173.
    Martusevich, A. K., Solov’eva, A. G., Peretyagin, S. P., and Davydyuk, A. V. (2014) Effect of dinitrosyl iron complexes on blood metabolic parameters from animals with experimental thermal injury, Biofizika, 59, 1173–1179.PubMedGoogle Scholar
  174. 174.
    Bryszewska, M. (1988) Interaction of normal and glycated human haemoglobin with erythrocyte membranes from normal and diabetic individuals, J. Clin. Chem. Clin. Biochem., 26, 809–813.PubMedGoogle Scholar
  175. 175.
    Nasybullina, E. I., Nikitaev, V. G., Pronichev, A. N., Blindar, V. N., Kosmachevskaya, O. V., and Topunov, A. F. (2015) Expert diagnostic system for hemoglobinopathies using the data on blood, erythrocyte, and hemoglobin state, Bull. Lebedev Phys. Inst., 42, 206–208.CrossRefGoogle Scholar
  176. 176.
    De Henau, S., and Braeckman, B. P. (2016) Globin–based redox signaling, Worm, 5, e1184390.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Burr, A. H., Hunt, P., Wagar, D. R., Dewilde, S., Blaxter, M. L., Vanfleteren, J. R., and Moens, L. (2000) A hemoglobin with an optical function, J. Biol. Chem., 275, 4810–4815.CrossRefPubMedGoogle Scholar
  178. 178.
    Brooks, J. (1937) The action of nitrite on haemoglobin in the absence of oxygen, Proc. Royal Soc. Lond. Ser. B Biol. Sci., 123, 368–382.Google Scholar
  179. 179.
    Gladwin, M. T. (2004) Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion, J. Clin. Invest., 113, 19–21.PubMedGoogle Scholar

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© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  1. 1.Bach Institute of Biochemistry, Research Center of BiotechnologyRussian Academy of SciencesMoscowRussia

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