864
Views
14
CrossRef citations to date
0
Altmetric
Review Article

Erythrocytes as a preferential target of oxidative stress in blood

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 781-799 | Received 17 Jun 2020, Accepted 04 Jan 2021, Published online: 17 Jan 2021

References

  • Tanaka K, Mizushima T, Saeki Y. The proteasome: molecular machinery and pathophysiological roles. Biol Chem. 2012;393(4):217–234.
  • Morishita H, Mizushima N. Diverse cellular roles of autophagy. Annu Rev Cell Dev Biol. 2019;35:453–475.
  • Roux-Dalvai F, Gonzalez de Peredo A, Simó C, et al. Extensive analysis of the cytoplasmic proteome of human erythrocytes using the peptide ligand library technology and advanced mass spectrometry. Mol Cell Proteomics. 2008;7(11):2254–2269.
  • Rifkind JM, Nagababu E. Hemoglobin redox reactions and red blood cell aging. Antioxid Redox Signal. 2013;18(17):2274–2283.
  • Cox AG, Winterbourn CC, Hampton MB. Measuring the redox state of cellular peroxiredoxins by immunoblotting. Methods Enzymol. 2010;474:51–66.
  • Davies MJ, Fu S, Wang H, et al. Stable markers of oxidant damage to proteins and their application in the study of human disease. Free Radic Biol Med. 1999;27(11–12):1151–1163.
  • Grune T. Oxidized protein aggregates: formation and biological effects. Free Radic Biol Med. 2020;150:120–124.
  • Zivot A, Lipton JM, Narla A, et al. Erythropoiesis: insights into pathophysiology and treatments in 2017. Mol Med. 2018;24(1):11.
  • Zhen R, Moo C, Zhao Z, et al. Wdr26 regulates nuclear condensation in developing erythroblasts. Blood. 2020;135(3):208–219.
  • Thom CS, Traxler EA, Khandros E, et al. Trim58 degrades dynein and regulates terminal erythropoiesis. Dev Cell. 2014;30(6):688–700.
  • Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1):9–14.
  • Chen CY, Pajak L, Tamburlin J, et al. The effect of proteasome inhibitors on mammalian erythroid terminal differentiation. Exp Hematol. 2002;30(7):634–639.
  • Nguyen AT, Prado MA, Schmidt PJ, et al. UBE2O remodels the proteome during terminal erythroid differentiation. Science. 2017;357(6350):eaan0218.
  • Bauer C, Kurtz A. Oxygen sensing in the kidney and its relation to erythropoietin production. Annu Rev Physiol. 1989;51:845–856.
  • Sato Y, Yanagita M. Renal anemia: from incurable to curable. Am J Physiol Renal Physiol. 2013;305(9):F1239–F1248.
  • Canavesi E, Alfieri C, Pelusi S, et al. Hepcidin and HFE protein: iron metabolism as a target for the anemia of chronic kidney disease. World J Nephrol. 2012;1(6):166–176.
  • Pagani A, Nai A, Silvestri L, et al. Hepcidin and anemia: a tight relationship. Front Physiol. 2019;10:1294.
  • Ganz T. Anemia of inflammation. N Engl J Med. 2019;381(12):1148–1157.
  • Fraenkel PG. Anemia of inflammation: a review. Med Clin North Am. 2017;101(2):285–296.
  • Brissot P, Pietrangelo A, Adams PC, et al. Haemochromatosis. Nat Rev Dis Primers. 2018;4:18016.
  • Lippi G, Mattiuzzi C. Updated worldwide epidemiology of inherited erythrocyte disorders. Acta Haematol. 2020;143(3):196–197.
  • Grace RF, Glader B. Red blood cell enzyme disorders. Pediatr Clin North Am. 2018;65(3):579–595.
  • Bianchi P, Fermo E, Lezon-Geyda K, et al. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020;95(5):472–482.
  • Grace RF, Bianchi P, van Beers EJ, et al. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018;131(20):2183–2192.
  • Grace RF, Mark Layton D, Barcellini W. How we manage patients with pyruvate kinase deficiency. Br J Haematol. 2019;184(5):721–734.
  • Beutler E. Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood. 2008;111(1):16–24.
  • Mason PJ, Bautista JM, Gilsanz F. G6PD deficiency: the genotype-phenotype association. Blood Rev. 2007;21(5):267–283.
  • Pandolfi PP, Sonati F, Rivi R, et al. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J. 1995;14(21):5209–5215.
  • Cheah FC, Peskin AV, Wong FL, et al. Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants. FASEB J. 2014;28(7):3205–3210.
  • Ware RE, de Montalembert M, Tshilolo L, et al. Sickle cell disease. Lancet. 2017;390(10091):311–323.
  • Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018;391(10116):155–167.
  • Longo L, Vanegas OC, Patel M, et al. Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal. EMBO J. 2002;21(16):4229–4239.
  • Pretsch W, Charles DJ, Merkle S. X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus. Biochem Genet. 1988;26(1–2):89–103.
  • Hecker PA, Leopold JA, Gupte SA, et al. Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease. Am J Physiol Heart Circ Physiol. 2013;304(4):H491–H500.
  • Sanders S, Smith DP, Thomas GA, et al. A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency. Mutat Res. 1997;374(1):79–87.
  • Bhattacharya D, Saha S, Basu S, et al. Differential regulation of redox proteins and chaperones in HbEβ-thalassemia erythrocyte proteome. Proteomics Clin Appl. 2010;4(5):480–488.
  • De Franceschi L, Bertoldi M, De Falco L, et al. Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis. Haematologica. 2011;96(11):1595–1604.
  • Lithanatudom P, Smith DR. Analysis of protein profiling studies of β-thalassemia/Hb E disease. Proteomics Clin Appl. 2016;10(11):1093–1102.
  • Romanello KS, Teixeira KKL, Silva JPMO, Nagamatsu ST, et al. Global analysis of erythroid cells redox status reveals the involvement of Prdx1 and Prdx2 in the severity of beta thalassemia. PLoS One. 2018;13(12):e0208316.
  • Matte A, Low PS, Turrini F, et al. Peroxiredoxin-2 expression is increased in beta-thalassemic mouse red cells but is displaced from the membrane as a marker of oxidative stress. Free Radic Biol Med. 2010;49(3):457–466.
  • Matte A, De Falco L, Federti E, et al. Peroxiredoxin-2: a novel regulator of iron homeostasis in ineffective erythropoiesis. Antioxid Redox Signal. 2018;28(1):1–14.
  • May C, Rivella S, Chadburn A, et al. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood. 2002;99(6):1902–1908.
  • De Franceschi L, Bertoldi M, Matte A, et al. Oxidative stress and β-thalassemic erythroid cells behind the molecular defect. Oxid Med Cell Longev. 2013;2013:985210.
  • Rund D. Thalassemia 2016: modern medicine battles an ancient disease. Am J Hematol. 2016;91(1):15–21.
  • Lisowski L, Sadelain M. Current status of globin gene therapy for the treatment of beta-thalassaemia. Br J Haematol. 2008;141(3):335–345.
  • Nagel RL, Fleming AF. Genetic epidemiology of the beta s gene. Baillieres Clin Haematol. 1992;5(2):331–365.
  • Alabdulaali MK. Sickle cell disease patients in eastern province of Saudi Arabia suffer less severe acute chest syndrome than patients with African haplotypes. Ann Thorac Med. 2007;2(4):158–162.
  • Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750–760.
  • Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;376(16):1561–1573.
  • Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;8(12):1383–1389.
  • Kassa T, Jana S, Strader MB, et al. Sickle cell hemoglobin in the ferryl state promotes βCys-93 oxidation and mitochondrial dysfunction in epithelial lung cells (E10). J Biol Chem. 2015;290(46):27939–27958.
  • Jana S, Strader MB, Meng F, et al. Hemoglobin oxidation-dependent reactions promote interactions with band 3 and oxidative changes in sickle cell-derived microparticles. JCI Insight. 2018;3(21):120451.
  • Zhang Y, Dai Y, Wen J, et al. Detrimental effects of adenosine signaling in sickle cell disease. Nat Med. 2011;17(1):79–86.
  • Zhang Y, Berka V, Song A, et al. Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression. J Clin Invest. 2014;124(6):2750–2761.
  • Sun K, Zhang Y, Bogdanov MV, et al. Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity. Blood. 2015;125(10):1643–1652.
  • Sun K, D’Alessandro A, Ahmed MH, et al. Structural and functional insight of sphingosine 1-phosphate-mediated pathogenic metabolic reprogramming in sickle cell disease. Sci Rep. 2017;7(1):15281.
  • Fiesco-Roa MO, Giri N, McReynolds LJ, et al. Genotype-phenotype associations in Fanconi anemia: a literature review. Blood Rev. 2019;37:100589.
  • Kumari U, Ya Jun W, Huat Bay B, et al. Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi anemia cells. Oncogene. 2014;33(2):165–172.
  • Hadjur S, Ung K, Wadsworth L, et al. Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase. Blood. 2001;98(4):1003–1011.
  • Mukhopadhyay SS, Leung KS, Hicks MJ, et al. Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia. J Cell Biol. 2006;175(2):225–235.
  • Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 4th ed. Oxford (UK): Oxford University Press; 2007.
  • Winterbourn CC. Oxidative reactions of hemoglobin. Methods Enzymol. 1990;186:265–272.
  • Johnson RM, Goyette G, Jr, Ravindranath Y, et al. Hemoglobin autoxidation and regulation of endogenous H2O2 levels in erythrocytes. Free Radic Biol Med. 2005;39(11):1407–1417.
  • Umbreit J. Methemoglobin-it’s not just blue: a concise review. Am J Hematol. 2007;82(2):134–144.
  • Tejero J, Shiva S, Gladwin MT. Sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev. 2019;99(1):311–379.
  • Kim-Shapiro DB, Schechter AN, Gladwin MT. Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics. Arterioscler Thromb Vasc Biol. 2006;26(4):697–705.
  • Chen K, Piknova B, Pittman RN, et al. Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes. Nitric Oxide. 2008;18(1):47–60.
  • Jia L, Bonaventura C, Bonaventura J, et al. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature. 1996;380(6571):221–226.
  • Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87(1):315–424.
  • Cortese-Krott MM, Kelm M. Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol. 2014;2:251–258.
  • Radi R. Peroxynitrite, a stealthy biological oxidant. J Biol Chem. 2013;288(37):26464–26472.
  • Fibach E, Rachmilewitz E. The role of oxidative stress in hemolytic anemia. Curr Mol Med. 2008;8(7):609–619.
  • Voskou S, Aslan M, Fanis P, et al. Oxidative stress in β-thalassaemia and sickle cell disease. Redox Biol. 2015;6:226–239.
  • Fujii J, Kurahashi T, Konno T, et al. Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and systemic lupus erythematosus. World J Nephrol. 2015;4(2):213–222.
  • Ito K, Hirao A, Arai F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12(4):446–451.
  • Rhee SG, Woo HA, Kil IS, et al. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J Biol Chem. 2012;287(7):4403–4410.
  • Fujii J, Ito JI, Zhang X, et al. Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice. J Clin Biochem Nutr. 2011;49(2):70–78.
  • McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244(22):6049–6055.
  • Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011;15(6):1583–1606.
  • Flynn JM, Melov S. SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic Biol Med. 2013;62:4–12.
  • Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem. 1995;64:97–112.
  • Tainer JA, Getzoff ED, Richardson JS, et al. Structure and mechanism of copper, zinc superoxide dismutase. Nature. 1983;306(5940):284–287.
  • Watanabe K, Shibuya S, Ozawa Y, et al. Superoxide dismutase 1 loss disturbs intracellular redox signaling, resulting in global age-related pathological changes. Biomed Res Int. 2014;2014:140165.
  • Meissner F, Molawi K, Zychlinsky A. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol. 2008;9(8):866–872.
  • Lei XG, Zhu JH, McClung JP, et al. Mice deficient in Cu,Zn-superoxide dismutase are resistant to acetaminophen toxicity. Biochem J. 2006;399(3):455–461.
  • Shirato T, Homma T, Lee J, et al. Oxidative stress caused by a SOD1 deficiency ameliorates thioacetamide-triggered cell death via CYP2E1 inhibition but stimulates liver steatosis. Arch Toxicol. 2017;91(3):1319–1333.
  • Reaume AG, Elliott JL, Hoffman EK, et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet. 1996;13(1):43–47.
  • Ho YS, Gargano M, Cao J, et al. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem. 1998;273(13):7765–7769.
  • Matzuk MM, Dionne L, Guo Q, et al. Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology. 1998;139(9):4008–4011.
  • Iuchi Y, Okada F, Onuma K, et al. Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production. Biochem J. 2007;402(2):219–227.
  • Starzyński RR, Canonne-Hergaux F, Willemetz A, et al. Haemolytic anaemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase. Biochem J. 2009;420(3):383–390.
  • Iuchi Y, Okada F, Takamiya R, et al. Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes. Biochem J. 2009;422(2):313–320.
  • Yoshihara D, Fujiwara N, Ookawara T, et al. Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice. Free Radic Biol Med. 2009;47(5):559–567.
  • Yoshihara D, Fujiwara N, Kato S, et al. Alterations in renal iron metabolism caused by a copper/zinc-superoxide dismutase deficiency. Free Radic Res. 2012;46(6):750–757.
  • Iuchi Y, Kibe N, Tsunoda S, et al. Implication of oxidative stress as a cause of autoimmune hemolytic anemia in NZB mice. Free Radic Biol Med. 2010;48(7):935–944.
  • Guo Z, Higuchi K, Mori M. Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Free Radic Biol Med. 2003;35(12):1645–1652.
  • Konno T, Otsuki N, Kurahashi T, et al. Reactive oxygen species exacerbate autoimmune hemolytic anemia in New Zealand Black mice. Free Radic Biol Med. 2013;65:1378–1384.
  • Otsuki N, Konno T, Kurahashi T, et al. The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice. Free Radic Res. 2016;50(7):793–800.
  • Homma T, Takeda Y, Sakahara S, et al. Heterozygous SOD1 deficiency in mice with an NZW background causes male infertility and an aberrant immune phenotype. Free Radic Res. 2019;53(11–12):1060–1072.
  • Toyokuni S, Ito F, Yamashita K, et al. Iron and thiol redox signaling in cancer: an exquisite balance to escape ferroptosis. Free Radic Biol Med. 2017;108:610–626.
  • Ursini F, Maiorino M. Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Radic Biol Med. 2020;152:175–185.
  • Attri S, Sharma N, Jahagirdar S, et al. Erythrocyte metabolism and antioxidant status of patients with Wilson disease with hemolytic anemia. Pediatr Res. 2006;59(4):593–597.
  • Culotta VC, Yang M, O’Halloran TV. Activation of superoxide dismutases: putting the metal to the pedal. Biochim Biophys Acta. 2006;1763(7):747–758.
  • Wong PC, Waggoner D, Subramaniam JR, et al. Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. Proc Natl Acad Sci USA. 2000;97(6):2886–2891.
  • Bertinato J, Sherrard L, Plouffe LJ. Decreased erythrocyte CCS content is a biomarker of copper overload in rats. Int J Mol Sci. 2010;11(7):2624–2635.
  • Lassi KC, Prohaska JR. Erythrocyte copper chaperone for superoxide dismutase is increased following marginal copper deficiency in adult and postweanling mice. J Nutr. 2012;142(2):292–297.
  • Seidl R, Cairns N, Lubec G. The brain in Down syndrome. J Neural Transm Suppl. 2001;61:247–261.
  • Hayashi Y, Homma K, Ichijo H. SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS. Adv Biol Regul. 2016;60:95–104.
  • Li Y, Huang TT, Carlson EJ, et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet. 1995;11(4):376–381.
  • Friedman JS, Rebel VI, Derby R, et al. Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant. J Exp Med. 2001;193(8):925–934.
  • Friedman JS, Lopez MF, Fleming MD, et al. SOD2-deficiency anemia: protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness. Blood. 2004;104(8):2565–2573.
  • Martin FM, Bydlon G, Friedman JS. SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress. Antioxid Redox Signal. 2006;8(7–8):1217–1225.
  • Mohanty JG, Nagababu E, Friedman JS, et al. SOD2 deficiency in hematopoietic cells in mice results in reduced red blood cell deformability and increased heme degradation. Exp Hematol. 2013;41(3):316–321.
  • Martin FM, Xu X, von Löhneysen K, et al. SOD2 deficient erythroid cells up-regulate transferrin receptor and down-regulate mitochondrial biogenesis and metabolism. PLoS One. 2011;6(2):e16894.
  • Fidler TP, Rowley JW, Araujo C, et al. Superoxide dismutase 2 is dispensable for platelet function. Thromb Haemost. 2017;117(10):1859–1867.
  • Mueller S, Riedel HD, Stremmel W. Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes. Blood. 1997;90(12):4973–4978.
  • Góth L, Nagy T. Inherited catalase deficiency: is it benign or a factor in various age related disorders? Mutat Res. 2013;753(2):147–154.
  • Nagy T, Paszti E, Kaplar M, et al. Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia. Mutat Res. 2015;772:10–14.
  • Ho YS, Xiong Y, Ma W, et al. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem. 2004;279(31):32804–32812.
  • Johnson RM, Ho YS, Yu DY, et al. The effects of disruption of genes for peroxiredoxin-2, glutathione peroxidase-1, and catalase on erythrocyte oxidative metabolism. Free Radic Biol Med. 2010;48(4):519–525.
  • Benhar M. Roles of mammalian glutathione peroxidase and thioredoxin reductase enzymes in the cellular response to nitrosative stress. Free Radic Biol Med. 2018;127:160–164.
  • Ho YS, Magnenat JL, Bronson RT, et al. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem. 1997;272(26):16644–16651.
  • Johnson RM, Goyette G, Jr, Ravindranath Y, et al. Red cells from glutathione peroxidase-1-deficient mice have nearly normal defenses against exogenous peroxides. Blood. 2000;96(5):1985–1988.
  • Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072.
  • Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell. 2018;172(3):409–422.
  • Rhee SG, Kil IS. Multiple functions and regulation of mammalian peroxiredoxins. Annu Rev Biochem. 2017;86:749–775.
  • Fujii J, Ikeda Y. Advances in our understanding of peroxiredoxin, a multifunctional, mammalian redox protein. Redox Rep. 2002;7(3):123–130.
  • Low FM, Hampton MB, Winterbourn CC. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid Redox Signal. 2008;10(9):1621–1630.
  • Taketani S, Adachi Y, Kohno H, et al. Molecular characterization of a newly identified heme-binding protein induced during differentiation of urine erythroleukemia cells. J Biol Chem. 1998;273(47):31388–31394.
  • Schröder E, Littlechild JA, Lebedev AA, et al. Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 Å resolution. Structure. 2000;8(6):605–615.
  • Rhee SG, Woo HA. Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H2O2, and protein chaperones. Antioxid Redox Signal. 2011;15(3):781–794.
  • Yang KS, Kang SW, Woo HA, et al. Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid. J Biol Chem. 2002;277(41):38029–38036.
  • Moon JC, Hah YS, Kim WY, et al. Oxidative stress-dependent structural and functional switching of a human 2-Cys peroxiredoxin isotype II that enhances HeLa cell resistance to H2O2-induced cell death. J Biol Chem. 2005;280(31):28775–28784.
  • Lee CK, Kim HJ, Lee YR, et al. Analysis of peroxiredoxin decreasing oxidative stress in hypertensive aortic smooth muscle. Biochim Biophys Acta. 2007;1774(7):848–855.
  • Lim JC, Choi HI, Park YS, et al. Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity. J Biol Chem. 2008;283(43):28873–28880.
  • Biteau B, Labarre J, Toledano MB. ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature. 2003;425(6961):980–984.
  • Woo HA, Jeong W, Chang TS, et al. Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-cys peroxiredoxins. J Biol Chem. 2005;280(5):3125–3128.
  • Cho CS, Lee S, Lee GT, et al. Irreversible inactivation of glutathione peroxidase 1 and reversible inactivation of peroxiredoxin II by H2O2 in red blood cells. Antioxid Redox Signal. 2010;12(11):1235–1246.
  • O’Neill JS, Reddy AB. Circadian clocks in human red blood cells. Nature. 2011;469(7331):498–503.
  • Cho CS, Yoon HJ, Kim JY, et al. Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells. Proc Natl Acad Sci USA. 2014;111:1–6.
  • Low FM, Hampton MB, Peskin AV, et al. Peroxiredoxin 2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in the erythrocyte. Blood. 2007;109(6):2611–2617.
  • Homma T, Okano S, Lee J, et al. SOD1 deficiency induces the systemic hyperoxidation of peroxiredoxin in the mouse. Biochem Biophys Res Commun. 2015;463(4):1040–1046.
  • Homma T, Kurahashi T, Lee J, et al. SOD1 deficiency decreases proteasomal function, leading to the accumulation of ubiquitinated proteins in erythrocytes. Arch Biochem Biophys. 2015;583:65–72.
  • Lee TH, Kim SU, Yu SL, et al. Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood. 2003;101(12):5033–5038.
  • Han YH, Kwon T, Kim SU, et al. Peroxiredoxin I deficiency attenuates phagocytic capacity of macrophage in clearance of the red blood cells damaged by oxidative stress. BMB Rep. 2012;45(10):560–564.
  • Bayer SB, Low FM, Hampton MB, et al. Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane. Free Radic Res. 2016;50(12):1329–1339.
  • Rocha S, Vitorino RM, Lemos-Amado FM, et al. Presence of cytosolic peroxiredoxin 2 in the erythrocyte membrane of patients with hereditary spherocytosis. Blood Cells Mol Dis. 2008;41(1):5–9.
  • Rocha S, Costa E, Rocha-Pereira P, et al. Erythrocyte membrane protein destabilization versus clinical outcome in 160 Portuguese hereditary spherocytosis patients. Br J Haematol. 2010;149(5):785–794.
  • Rocha S, Rocha-Pereira P, Cleto E, et al. Linkage of typically cytosolic peroxidases to erythrocyte membrane - a possible mechanism of protection in hereditary spherocytosis. Biochim Biophys Acta Biomembr. 2020;1862(3):183172.
  • Neumann CA, Krause DS, Carman CV, et al. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 2003;424(6948):561–565.
  • Uwayama J, Hirayama A, Yanagawa T, et al. Tissue Prx I in the protection against Fe-NTA and the reduction of nitroxyl radicals. Biochem Biophys Res Commun. 2006;339(1):226–231.
  • Han YH, Kim SU, Kwon TH, et al. Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability. Biochem Biophys Res Commun. 2012;426(3):427–432.
  • Shang F, Taylor A. Ubiquitin-proteasome pathway and cellular responses to oxidative stress. Free Radic Biol Med. 2011;51(1):5–16.
  • Davies KJ. Degradation of oxidized proteins by the 20S proteasome. Biochimie. 2001;83(3–4):301–310.
  • Orlowski M, Wilk S. Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Arch Biochem Biophys. 2000;383(1):1–16.
  • Pacifici RE, Salo DC, Davies KJ. Macroxyproteinase (M.O.P.): a 670 kDa proteinase complex that degrades oxidatively denatured proteins in red blood cells. Free Radic Biol Med. 1989;7(5):521–536.
  • Pacifici RE, Kono Y, Davies KJ. Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasome. J Biol Chem. 1993;268(21):15405–15411.
  • Khandros E, Weiss MJ. Protein quality control during erythropoiesis and hemoglobin synthesis. Hematol Oncol Clin North Am. 2010;24(6):1071–1088.
  • Khandros E, Thom CS, D’Souza J, et al. Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia. Blood. 2012;119(22):5265–5275.
  • Basu A, Saha S, Karmakar S, et al. 2D DIGE based proteomics study of erythrocyte cytosol in sickle cell disease: altered proteostasis and oxidative stress. Proteomics. 2013;13(21):3233–3242.
  • Cho CS, Kato GJ, Yang SH, et al. Hydroxyurea-induced expression of glutathione peroxidase 1 in red blood cells of individuals with sickle cell anemia. Antioxid Redox Signal. 2010;13(1):1–11.
  • Biondani A, Turrini F, Carta F, et al. Heat-shock protein-27, -70 and peroxiredoxin-II show molecular chaperone function in sickle red cells: evidence from transgenic sickle cell mouse model. Proteomics Clin Appl. 2008;2(5):706–719.
  • Majetschak M, Sorell LT. Immunological methods to quantify and characterize proteasome complexes: development and application. J Immunol Methods. 2008;334(1–2):91–103.
  • Reinhecke T, Sitte N, Ullrich O, et al. Comparative resistance of the 20S and 26S proteasome to oxidative stress. Biochem J. 1998;335(3):637–642.
  • Homma T, Fujii J. Emerging connections between oxidative stress, defective proteolysis, and metabolic diseases. Free Radic Res. 2020; Apr 20:1–16.
  • Waite KA, De-La Mota-Peynado A, Vontz G, et al. Starvation induces proteasome autophagy with different pathways for core and regulatory particles. J Biol Chem. 2016;291(7):3239–3253.
  • Chirico EN, Pialoux V. Role of oxidative stress in the pathogenesis of sickle cell disease. IUBMB Life. 2012;64(1):72–80.
  • Warang P, Homma T, Pandya R, et al. Potential involvement of ubiquitin-proteasome system dysfunction associated with oxidative stress in the pathogenesis of sickle cell disease. Br J Haematol. 2018;182(4):559–566.
  • Pullarkat V, Meng Z, Tahara SM, et al. Proteasome inhibition induces both antioxidant and hb f responses in sickle cell disease via the nrf2 pathway. Hemoglobin. 2014;38(3):188–195.
  • Telen MJ. Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease. Blood. 2016;127(7):810–819.
  • Costa FC, da Cunha AF, Fattori A, et al. Gene expression profiles of erythroid precursors characterise several mechanisms of the action of hydroxycarbamide in sickle cell anaemia. Br J Haematol. 2007;136(2):333–342.
  • Cokic VP, Smith RD, Beleslin-Cokic BB, et al. Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. J Clin Invest. 2003;111(2):231–239.
  • Cokic VP, Beleslin-Cokic BB, Noguchi CT, et al. Hydroxyurea increases eNOS Protein levels through inhibition of proteasome activity. Nitric Oxide. 2007;16(3):371–379.
  • Huang J, Sommers EM, Kim-Shapiro DB, et al. Horseradish peroxidase catalyzed nitric oxide formation from hydroxyurea. J Am Chem Soc. 2002;124(13):3473–3480.
  • Huang J, Kim-Shapiro DB, King SB. Catalase-mediated nitric oxide formation from hydroxyurea. J Med Chem. 2004;47(14):3495–3501.
  • Italia K, Chandrakala S, Ghosh K, et al. Can hydroxyurea serve as a free radical scavenger and reduce iron overload in β-thalassemia patients? Free Radic Res. 2016;50(9):959–965.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.