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Role of Haptoglobin in Protection from the Toxic Effects of Extracellular Hemoglobin in Various Pathologies

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Abstract

The review presents modern domestic and foreign published data on the blood plasma protein haptoglobin, its structure, synthesis, function, and interaction with hemoglobin. The ability of haptoglobin in interaction with hemoglobin to reduce the toxic effect of the latter is shown. Clinical studies of such interaction in various pathological conditions such as diabetes mellitus, sickle cell anemia, malaria, and sepsis are described. It is noted that the development of new haptoglobin derivatives can contribute to the prevention of hemoglobin toxicity in hemolytic diseases.

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REFERENCES

  1. Alayash, A.I.A., Andersen, F.C.B., Maestrup, S.K., and Bulow, L., Haptoglobin: The hemoglobin detoxifier in plasma, Trends Biotechnol., 2013, vol. 31, no. 1, pp. 2–3.

    Article  CAS  PubMed  Google Scholar 

  2. Andersen, C.B.F., Stødkilde, K., Sæderup, K.L., et al., Haptoglobin, Antioxid. Redox Signaling, 2017, vol. 26, no. 14, pp. 814–831.

    Article  CAS  Google Scholar 

  3. Asleh, R., Guetta, J., Kalet-Litman, S., et al., Haptoglobin genotype- and diabetes-dependent differences in iron-mediated oxidative stress in vitro and in vivo, Circ. Res., 2005, vol. 96, no. 4, pp. 435–441.

    Article  CAS  PubMed  Google Scholar 

  4. Belcher, D.A., Munoz, C., Pires, I.S., et al., Apohemoglobin–haptoglobin complexes attenuate the hypertensive response to low-molecular-weight polymerized hemoglobin, Blood Adv., 2020, vol. 4, no. 12, pp. 2739–2750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Buechler, P.W., Humar, R., and Schaer, D.J., Haptoglobin therapeutics and compartmentalization of cell-free hemoglobin toxicity, Trends Mol. Med., 2020, vol. 26, no. 7, pp. 683–697.

    Article  Google Scholar 

  6. Cahill, L., Levy, A., Chiuve, E., et al., Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin, J. Am. Coll. Cardiol., 2013, vol. 61, pp. 728–737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Carter, K. and Worwood, M., Haptoglobin: Review of the major allele frequencies worldwide and their association with diseases, Int. J. Lab. Hematol., 2007, vol. 29, no. 2, pp. 92–110.

    Article  PubMed  Google Scholar 

  8. Deckmyn, O., Poynard, T., Bedossa, P., et al., Clinical interest of alpha-2 macroglobulin, apolipoprotein a1, and haptoglobin in patients with non-alcogolic fatty liver disease, with and without type 2 diabetes, before or during COVID-19, Biomedicines, 2022, vol. 10, no. 3, p. 699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dhaliwal, G., Cornett, P., and Tierney, L., Hemolytic anemia, Am. Fam. Physician, 2004, vol. 69, no. 11, pp. 2599–2606.

    PubMed  Google Scholar 

  10. Di Masi, A., De Simone, G., Ciaccio, C., et al., Haptoglobin: From hemoglobin scavenging to human healt, Mol. Aspects Med., 2020, vol. 73, p. 100851.

    Article  CAS  PubMed  Google Scholar 

  11. Etzerodt, A. and Moestrup, S.K., CD163 and inflammation: Biological, diagnostic, and therapeutic aspects, Antioxid. Redox Signaling, 2013, vol. 18, no. 17, pp. 2352–2363.

    Article  CAS  Google Scholar 

  12. Fotsing, C.B.K., Pieme, C.A., Nya, P.C.B.C., et al., Haptoglobin gene polymorphism among sickle cell patients in West Cameroon: Hematological and clinical implication, Adv. Hematol., 2021, vol. 2021, p. 6939413.

    Google Scholar 

  13. Garland, P., Morton, M., Haskins, W., et al., Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin, Brain Commun., 2020, vol. 2, no. 1, p. fcz053.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gbotosho, O., Kapetanaki, M., and Kato, J., The worst things in life are free: The role of free hame in sickle cell disease, Front. Immunol., 2021, vol. 11, p. 561917.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Golubeva, M.G., Osmotic resistance of erythrocytes, methods of determinationand correction, value at different pathologies, Usp. Sovrem. Biol., 2019, vol. 139, no. 5, pp. 446–456.

    Google Scholar 

  16. Golubeva, M.G., Influence of exercise on the functional state of erythrocytes membranes, Sports Med., 2020, vol. 10, no. 2, pp. 55–64.

    Article  Google Scholar 

  17. Graw, J.A., Yu, B., Rezoagli, E., et al., Endothelial dysfunction inhibits the ability of haptoglobin to prevent hemoglobin-induced hypertension, Am. J. Physiol.: Heart Circ. Physiol., 2017, vol. 312, no. 6, pp. H1120–H1127.

    PubMed  Google Scholar 

  18. Graw, J.A., Baron, D.M., and Francis, R.C.E., The relevance of hemolysis in anesthesia and intensive care medicine, Anasthesiol., Intensivmed., Notfallmed., Schmerzther., 2018, vol. 53, no. 4, pp. 296–305.

    PubMed  Google Scholar 

  19. Guéye, P.M., Glasser, N., Férard, G., and Lessinger, J.-M., Influence of human haptoglobin polymorphism on oxidative stress induced by free hemoglobin on red blood cells, Clin. Chem. Lab. Med., 2006, vol. 44, no. 5, pp. 542–547.

    Article  PubMed  Google Scholar 

  20. Hämäläinen, P., Saltevo, J., Kautiainen, H., et al., Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: A case control study, Cardiovasc. Diabetol., 2012, vol. 11, p. 116.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Langlois, M.R. and Delanghe, J.R., Biological and clinical significance of haptoglobin polymorphism in humans, Clin. Chem., 1996, vol. 42, no. 10, pp. 1589–1600.

    Article  CAS  PubMed  Google Scholar 

  22. Levy, A.P., Asleh, R., Blum, S., et al., Haptoglobin: Basic and clinical aspects, Antioxid. Redox. Signaling, 2010, vol. 12, no. 2, pp. 293–304.

    Article  CAS  Google Scholar 

  23. Lippi, G., Schena, F.G., Salvagno, G.L., et al., Foot-strike haemolysis after a 60-km ultramarathon, Blood Transfus., 2012, vol. 10, no. 3, pp. 377–383.

    PubMed  PubMed Central  Google Scholar 

  24. Lippi, G. and Sanchis-Gomar, F., Epidemiological, biological and clinical update on exercise-induced hemolysis, Ann. Transl. Med., 2019, vol. 7, no. 12, p. 270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maffei, M., Barone, I., Scabia, G., and Santini, F., The multifaceted haptoglobin in the context of adipose tissue and metabolism, Endocr. Rev., 2016, vol. 37, no. 4, pp. 403–416.

    Article  CAS  PubMed  Google Scholar 

  26. Meher, S., Mohanty, P.K., Patel, S., et al., Haptoglobin genotypes associated with vaso-occlusive crisis in sickle anemia patients of eastern india, Hemoglobin, 2021, vol. 45, pp. 358–364.

    Article  CAS  PubMed  Google Scholar 

  27. Naryzny, S.N. and Legina, O.K., Haptoglobin as a biomarker, Biochem. (Moscow), Suppl. Ser. B, 2021, vol. 15, no. 3, pp. 184–198.

    Article  CAS  Google Scholar 

  28. Nishiie-Yano, R., Hirayama, S., Tamura, M., et al., Hemolysis is responsible for elevation of serum iron concentration after regular exercises in judo athletes, Biol. Trace Elem. Res., 2020, vol. 197, no. 1, pp. 63–69.

    Article  CAS  PubMed  Google Scholar 

  29. Polticelli, F., Bocedi, A., Minervini, G., and Ascenzi, P., Human haptoglobin structure and function—A molecular modelling study, FEBS J., 2008, vol. 275, no. 22, pp. 5648–5656.

    Article  CAS  PubMed  Google Scholar 

  30. Rodrigues, K.F., Pietrani, N.T., Carvalho, L.M.L., et al., Haptoglobin levels are influenced by Hp1–Hp2 polymorphism, obesity, inflammation, and hypertension in type 2 diabetes mellitus, Endocrinol., Diabetes Nutr., 2019, vol. 66, no. 2, pp. 99–107.

    Article  Google Scholar 

  31. Sadrzadeh, S. and Bozorgmehr, J., Haptoglobin phenotypes in health and disorders, Am J. Clin. Pathol., 2004, vol. 121, suppl. S97–S104.

  32. Sarpong-Kumankomah, S.K.B., Knox, K.B., Kelly, M.E., et al., Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age, PLoS One, 2022, vol. 17, no. 1, p. e0262160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Schaer, C.A., Deuel, J.W., Bittermann, A.G., et al., Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage, Cell Death. Differ., 2013, vol. 20, no. 11, pp. 1569–1579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shih, A., MacFarlane, A., and Verhovsek M., Haptoglobin testing in hemolysis: Measurement and interpretation, Am. J. Hematol., 2014, vol. 89, no. 4, pp. 443–447.

    Article  CAS  PubMed  Google Scholar 

  35. Shutov, M.E., Haptoglobin—What Is It? Norm Indicators. http://www.ayzdorov.ru/ttermini_gaptoglobin.php.

  36. Simon, A., Schneider, N., Gillery, Ph., and Oudart, J.-B., Clinical and biological features of haptoglobin phenotypes, Ann. Biol. Clin., 2020, vol. 78, no. 5, pp. 493–498.

    CAS  Google Scholar 

  37. Smetanina, N.S., Talassemia. https://rare-diseases.ru/docs/ talas.pdf.

  38. Tang, K., Huang, S., Cheng, T., et al., Haptoglobin phenotype influences the effectiveness of diet-induced weight loss in middle-age abdominally obese women with metabolic abnormalities, Clin. Nutr., 2020, vol. 39, no. 1, pp. 225–233.

    Article  CAS  PubMed  Google Scholar 

  39. van Avondt, K., Nur, E., and Zeerleder, S., Mechanisms of haemolysis-induced kidney injury, Nat. Rev. Nephrol., 2019, vol. 15, no. 11, pp. 671–692.

    Article  CAS  PubMed  Google Scholar 

  40. Wassel, J., Haptoglobin: Function and polymorphism, Clin. Lab., 2000, vol. 46, nos. 11–12, pp. 547–552.

    Google Scholar 

  41. Yaǧci, S., Serin, E., Acicbe, O., et al., The relationship between serum erythropoietin, hepcidin, and haptoglobin levels with disease severity and other biochemical values in patients with COVID-19, Int. J. Lab. Hematol., 2021, vol. 43, no. 1 (suppl.), pp. 142–151.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yalamanoglu, A., Deuel, J.W., Hunt, R.C., et al., Depletion of haptoglobin and hemopexin promote hemoglobin-mediated lipoprotein oxidation in sickle cell disease, Am. J. Physiol. Lung Cell. Mol. Physiol., 2018, vol. 315, no. 5, pp. L765–L774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Faculty of Biology, Moscow State University, 119991, Moscow, Russia

    M. G. Golubeva

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Statement on the welfare of animals. All experiments were carried out in accordance with the ethical principles and regulations recommended by the European Science Foundation (ESF) and with the declaration of humane treatment of animals.

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Golubeva, M.G. Role of Haptoglobin in Protection from the Toxic Effects of Extracellular Hemoglobin in Various Pathologies. Biol Bull Rev 13, 293–300 (2023). https://doi.org/10.1134/S2079086423040047

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