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Effect of saponin on erythrocytes

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Abstract

Saponins, naturally occurring glycosides and triterpene glycosides in plants, are considered useful in the prophylaxis and treatment of several disorders, including malignancy. The effect of these substances is partly attributable to induction of both apoptosis and necrosis. Saponin has previously been shown to trigger hemolysis. Erythrocytes may avoid hemolysis by entering programmed cell death or eryptosis, characterized by cell shrinkage and cell membrane scrambling, leading to phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase of cytosolic Ca2+ activity ([Ca2+] i ). The present study explored, whether exposure of human erythrocytes to saponin modifies [Ca2+] i , ceramide formation, hemolysis, and eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, hemolysis from hemoglobin release, [Ca2+] i from Fluo3-fluorescence, and ceramide utilizing specific antibodies. A 24 h exposure to saponin (15 µg/ml) resulted in a significant increase of annexin V binding and a significant stimulation of hemolysis. Saponin (15 µg/ml) further increased [Ca2+] i and ceramide formation. Annexin V binding was significantly blunted but not abrogated in the nominal absence of extracellular Ca2+. Saponin thus triggers cell membrane scrambling, an effect partially due to entry of extracellular Ca2+ and ceramide formation.

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References

  1. Cox JC, Sjolander A, Barr IG. ISCOMs and other saponin based adjuvants. Adv Drug Deliv Rev. 1998;32:247–71.

    Article  PubMed  Google Scholar 

  2. Ragupathi G, Gardner JR, Livingston PO, Gin DY. Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer. Expert Rev Vaccines. 2011;10:463–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Sjolander A, Cox JC. Uptake and adjuvant activity of orally delivered saponin and ISCOM vaccines. Adv Drug Deliv Rev. 1998;34:321–38.

    Article  CAS  PubMed  Google Scholar 

  4. Skene CD, Sutton P. Saponin-adjuvanted particulate vaccines for clinical use. Methods. 2006;40:53–9.

    Article  CAS  PubMed  Google Scholar 

  5. Sun HX, Xie Y, Ye YP. Advances in saponin-based adjuvants. Vaccine. 2009;27:1787–96.

    Article  CAS  PubMed  Google Scholar 

  6. He NW, Zhao Y, Guo L, Shang J, Yang XB. Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen. J Med Food. 2012;15:350–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bian D, Liu M, Li Y, Xia Y, Gong Z, Dai Y. Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress. J Biochem Mol Toxicol. 2012;26:399–406.

    Article  CAS  PubMed  Google Scholar 

  8. Wu W, Gao X, Xu X, Luo Y, Liu M, Xia Y, et al. Saponin-rich fraction from Clematis chinensis Osbeck roots protects rabbit chondrocytes against nitric oxide-induced apoptosis via preventing mitochondria impairment and caspase-3 activation. Cytotechnology. 2013;65:287–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Yu X, Wang LN, Du QM, Ma L, Chen L, You R, et al. Akebia Saponin D attenuates amyloid beta-induced cognitive deficits and inflammatory response in rats: involvement of Akt/NF-kappaB pathway. Behav Brain Res. 2012;235:200–9.

    Article  CAS  PubMed  Google Scholar 

  10. Yu X, Wang LN, Ma L, You R, Cui R, Ji D, et al. Akebia saponin D attenuates ibotenic acid-induced cognitive deficits and pro-apoptotic response in rats: involvement of MAPK signal pathway. Pharmacol Biochem Behav. 2012;101:479–86.

    Article  CAS  PubMed  Google Scholar 

  11. Zhao X, Cong X, Zheng L, Xu L, Yin L, Peng J. Dioscin, a natural steroid saponin, shows remarkable protective effect against acetaminophen-induced liver damage in vitro and in vivo. Toxicol Lett. 2012;214:69–80.

    Article  CAS  PubMed  Google Scholar 

  12. Waheed A, Barker J, Barton SJ, Owen CP, Ahmed S, Carew MA. A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells. Eur J Pharm Sci. 2012;47:464–73.

    Article  CAS  PubMed  Google Scholar 

  13. Chen PS, Shih YW, Huang HC, Cheng HW. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS One. 2011;6:e20164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Hassan SB, Gullbo J, Hu K, Berenjian S, Morein B, Nygren P. The Nanoparticulate Quillaja Saponin BBE is selectively active towards renal cell carcinoma. Anticancer Res. 2013;33:143–51.

    PubMed  Google Scholar 

  15. Hong SW, Jung KH, Lee HS, Son MK, Yan HH, Kang NS, et al. SB365, Pulsatilla saponin D targets c-Met and exerts antiangiogenic and anti-tumor activities. Carcinogenesis. 2013;34(9):2156–69.

    Article  CAS  PubMed  Google Scholar 

  16. Kim AD, Kang KA, Zhang R, Lim CM, Kim HS, Kim DH, et al. Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase. Environ Toxicol Pharmacol. 2010;30:134–40.

    Article  CAS  PubMed  Google Scholar 

  17. Xiao M, Dai X, He X, Zhou R, Zhang B, Hu G, et al. Paris saponin I induces G(2)/M cell cycle arrest and apoptosis in human gastric carcinoma SGC7901 cells. J Huazhong Univ Sci Technolog Med Sci. 2011;31:768–72.

    Article  PubMed  Google Scholar 

  18. Xiao X, Zou J, Bui-Nguyen TM, Bai P, Gao L, Liu J, et al. Paris Saponin II of Rhizoma Paridis: a novel inducer of apoptosis in human ovarian cancer cells. Biosci Trends. 2012;6:201–11.

    Article  CAS  PubMed  Google Scholar 

  19. Wang B, Chun J, Liu Y, Han L, Wang YS, Joo EJ, et al. Synthesis of novel diosgenyl saponin analogues and apoptosis-inducing activity on A549 human lung adenocarcinoma. Org Biomol Chem. 2012;10:8822–34.

    Article  CAS  PubMed  Google Scholar 

  20. Wang G, Huang W, He H, Fu X, Wang J, Zou K, et al. Growth inhibition and apoptosis-inducing effect on human cancer cells by RCE-4, a spirostanol saponin derivative from natural medicines. Int J Mol Med. 2013;31:219–24.

    PubMed  Google Scholar 

  21. Son MK, Jung KH, Hong SW, Lee HS, Zheng HM, Choi MJ, et al. SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway. Food Chem. 2013;136:26–33.

    Article  CAS  PubMed  Google Scholar 

  22. Lu D, Xia Y, Tong B, Zhang C, Pan R, Xu H, Yang X, Dai Y. In vitro anti-angiogenesis effects and active constituents of the saponin fraction from Gleditsia sinensis. Integr Cancer Ther. 2012. doi:10.1177/1534735412442377.

  23. Raju J, Mehta R. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin. Nutr Cancer. 2009;61:27–35.

    Article  CAS  PubMed  Google Scholar 

  24. Song JS, Lim KM, Kang S, Noh JY, Kim K, Bae ON, et al. Procoagulant and prothrombotic effects of the herbal medicine, Dipsacus asper and its active ingredient, dipsacus saponin C, on human platelets. J Thromb Haemost. 2012;10:895–906.

    Article  CAS  PubMed  Google Scholar 

  25. Lang E, Qadri SM, Lang F. Killing me softly: suicidal erythrocyte death. Int J Biochem Cell Biol. 2012;44:1236–43.

    Article  CAS  PubMed  Google Scholar 

  26. Lang PA, Kaiser S, Myssina S, Birka C, Weinstock C, Northoff H, et al. Effect of vibrio parahaemolyticus haemolysin on human erythrocytes. Cell Microbiol. 2004;6:391–400.

    Article  CAS  PubMed  Google Scholar 

  27. Lang PA, Beringer O, Nicolay JP, Amon O, Kempe DS, Hermle T, et al. Suicidal death of erythrocytes in recurrent hemolytic uremic syndrome. J Mol Med (Berl). 2006;84:378–88.

    Article  PubMed  Google Scholar 

  28. Foller M, Sopjani M, Koka S, Gu S, Mahmud H, Wang K, et al. Regulation of erythrocyte survival by AMP-activated protein kinase. FASEB J. 2009;23:1072–80.

    Article  PubMed  Google Scholar 

  29. Brugnara C, de Franceschi L, Alper SL. Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J Clin Invest. 1993;92:520–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Lang PA, Kaiser S, Myssina S, Wieder T, Lang F, Huber SM. Role of Ca2+-activated K+ channels in human erythrocyte apoptosis. Am J Physiol Cell Physiol. 2003;285:C1553–60.

    Article  CAS  PubMed  Google Scholar 

  31. Berg CP, Engels IH, Rothbart A, Lauber K, Renz A, Schlosser SF, et al. Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis. Cell Death Differ. 2001;8:1197–206.

    Article  CAS  PubMed  Google Scholar 

  32. Klarl BA, Lang PA, Kempe DS, Niemoeller OM, Akel A, Sobiesiak M, et al. Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion. Am J Physiol Cell Physiol. 2006;290:C244–53.

    Article  CAS  PubMed  Google Scholar 

  33. Bhavsar SK, Bobbala D, Xuan NT, Foller M, Lang F. Stimulation of suicidal erythrocyte death by alpha-lipoic acid. Cell Physiol Biochem. 2010;26:859–68.

    Article  CAS  PubMed  Google Scholar 

  34. Foller M, Mahmud H, Gu S, Wang K, Floride E, Kucherenko Y, et al. Participation of leukotriene C(4) in the regulation of suicidal erythrocyte death. J Physiol Pharmacol. 2009;60:135–43.

    CAS  PubMed  Google Scholar 

  35. Lau IP, Chen H, Wang J, Ong HC, Leung KC, Ho HP, et al. In vitro effect of CTAB- and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology. 2012;6:847–56.

    Article  CAS  PubMed  Google Scholar 

  36. Maellaro E, Leoncini S, Moretti D, Del Bello B, Tanganelli I, De Felice C, et al. Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients. Acta Diabetol. 2013;50(4):489–95.

    Article  CAS  PubMed  Google Scholar 

  37. Foller M, Feil S, Ghoreschi K, Koka S, Gerling A, Thunemann M, et al. Anemia and splenomegaly in cGKI-deficient mice. Proc Natl Acad Sci USA. 2008;105:6771–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Bhavsar SK, Gu S, Bobbala D, Lang F. Janus kinase 3 is expressed in erythrocytes, phosphorylated upon energy depletion and involved in the regulation of suicidal erythrocyte death. Cell Physiol Biochem. 2011;27:547–56.

    Article  CAS  PubMed  Google Scholar 

  39. Kucherenko Y, Zelenak C, Eberhard M, Qadri SM, Lang F. Effect of casein kinase 1alpha activator pyrvinium pamoate on erythrocyte ion channels. Cell Physiol Biochem. 2012;30:407–17.

    Article  CAS  PubMed  Google Scholar 

  40. Zelenak C, Eberhard M, Jilani K, Qadri SM, Macek B, Lang F. Protein kinase CK1alpha regulates erythrocyte survival. Cell Physiol Biochem. 2012;29:171–80.

    Article  CAS  PubMed  Google Scholar 

  41. Gatidis S, Zelenak C, Fajol A, Lang E, Jilani K, Michael D, et al. p38 MAPK activation and function following osmotic shock of erythrocytes. Cell Physiol Biochem. 2011;28:1279–86.

    Article  CAS  PubMed  Google Scholar 

  42. Zelenak C, Foller M, Velic A, Krug K, Qadri SM, Viollet B, et al. Proteome analysis of erythrocytes lacking AMP-activated protein kinase reveals a role of PAK2 kinase in eryptosis. J Proteome Res. 2011;10:1690–7.

    Article  CAS  PubMed  Google Scholar 

  43. Lupescu A, Shaik N, Jilani K, Zelenak C, Lang E, Pasham V, et al. Enhanced erythrocyte membrane exposure of phosphatidylserine following sorafenib treatment: an in vivo and in vitro study. Cell Physiol Biochem. 2012;30:876–88.

    Article  CAS  PubMed  Google Scholar 

  44. Shaik N, Lupescu A, Lang F. Sunitinib-sensitive suicidal erythrocyte death. Cell Physiol Biochem. 2012;30:512–22.

    Article  CAS  PubMed  Google Scholar 

  45. Auyeung KK, Woo PK, Law PC, Ko JK. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol. 2012;141:635–41.

    Article  CAS  PubMed  Google Scholar 

  46. Jaiaree N, Itharat A, Kumapava K. Cytotoxic saponin against lung cancer cells from Dioscorea birmanica Prain & Burkill. J Med Assoc Thai. 2010;93(Suppl 7):S192–7.

    PubMed  Google Scholar 

  47. Ji DB, Xu B, Liu JT, Ran FX, Cui JR. beta-Escin sodium inhibits inducible nitric oxide synthase expression via downregulation of the JAK/STAT pathway in A549 cells. Mol Carcinog. 2011;50:945–60.

    Article  CAS  PubMed  Google Scholar 

  48. Tin MM, Cho CH, Chan K, James AE, Ko JK. Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis. 2007;28:1347–55.

    Article  CAS  PubMed  Google Scholar 

  49. Kang JH, Han IH, Sung MK, Yoo H, Kim YG, Kim JS, et al. Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2. Cancer Lett. 2008;261:84–92.

    Article  CAS  PubMed  Google Scholar 

  50. Liu X-M, Zhao X, Gao E-Z, Zhao Y-L, Liu Z, Yu Z-G. Comparative pharmacokinetics of five saponins after intravenous administration of TSFS injection and TSFS injection plus TFFG in rats under different physiological states. J Pharm Anal. 2014;4:53–62. doi:10.1016/j.jpha.2013.03.004.

  51. Brand VB, Sandu CD, Duranton C, Tanneur V, Lang KS, Huber SM, et al. Dependence of Plasmodium falciparum in vitro growth on the cation permeability of the human host erythrocyte. Cell Physiol Biochem. 2003;13:347–56.

    Article  CAS  PubMed  Google Scholar 

  52. Bookchin RM, Ortiz OE, Lew VL. Activation of calcium-dependent potassium channels in deoxygenated sickled red cells. Prog Clin Biol Res. 1987;240:193–200.

    CAS  PubMed  Google Scholar 

  53. Harrison HE, Bunting H, Ordway NK, Albrink WS. The pathogenesis of the renal injury produced in the dog by hemoglobin or methemoglobin. J Exp Med. 1947;86:339–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Borst O, Abed M, Alesutan I, Towhid ST, Qadri SM, Foller M, et al. Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX. Am J Physiol Cell Physiol. 2012;302:C644–51.

    Article  CAS  PubMed  Google Scholar 

  55. Andrews DA, Low PS. Role of red blood cells in thrombosis. Curr Opin Hematol. 1999;6:76–82.

    Article  CAS  PubMed  Google Scholar 

  56. Closse C, Dachary-Prigent J, Boisseau MR. Phosphatidylserine-related adhesion of human erythrocytes to vascular endothelium. Br J Haematol. 1999;107:300–2.

    Article  CAS  PubMed  Google Scholar 

  57. Gallagher PG, Chang SH, Rettig MP, Neely JE, Hillery CA, Smith BD, et al. Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis. Blood. 2003;101:4625–7.

    Article  CAS  PubMed  Google Scholar 

  58. Pandolfi A, Di Pietro N, Sirolli V, Giardinelli A, Di Silvestre S, Amoroso L, et al. Mechanisms of uremic erythrocyte-induced adhesion of human monocytes to cultured endothelial cells. J Cell Physiol. 2007;213:699–709.

    Article  CAS  PubMed  Google Scholar 

  59. Wood BL, Gibson DF, Tait JF. Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations. Blood. 1996;88:1873–80.

    CAS  PubMed  Google Scholar 

  60. Chung SM, Bae ON, Lim KM, Noh JY, Lee MY, Jung YS, et al. Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes. Arterioscler Thromb Vasc Biol. 2007;27:414–21.

    Article  CAS  PubMed  Google Scholar 

  61. Zwaal RF, Comfurius P, Bevers EM. Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci. 2005;62:971–88.

    Article  CAS  PubMed  Google Scholar 

  62. Siddiqi MH, Siddiqi MZ, Ahn S, Kang S, Kim YJ, Sathishkumar N, et al. Ginseng saponins and the treatment of osteoporosis: mini literature review. J Ginseng Res. 2013;37:261–8.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Dinda B, Debnath S, Mohanta BC, Harigaya Y. Naturally occurring triterpenoid saponins. Chem Biodivers. 2010;7:2327–580.

    Article  CAS  PubMed  Google Scholar 

  64. Uzayisenga R, Ayeka PA, Wang Y. Anti-diabetic potential of panax notoginseng saponins (PNS): a review. Phytother Res. 2014;28(4):510–6.

    Article  PubMed  Google Scholar 

  65. Yuan CS, Wang CZ, Wicks SM, Qi LW. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res. 2010;34:160–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Tian X, Tang H, Lin H, Cheng G, Wang S, Zhang X. Saponins: the potential chemotherapeutic agents in pursuing new anti-glioblastoma drugs. Mini Rev Med Chem. 2013;13:1709–24.

    Article  CAS  PubMed  Google Scholar 

  67. Man S, Gao W, Zhang Y, Huang L, Liu C. Chemical study and medical application of saponins as anti-cancer agents. Fitoterapia. 2010;81:703–14.

    Article  CAS  PubMed  Google Scholar 

  68. Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev. 2010;9:425–74.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Abed M, Towhid ST, Mia S, Pakladok T, Alesutan I, Borst O, et al. Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells. Am J Physiol Cell Physiol. 2012;303:C991–9.

    Article  CAS  PubMed  Google Scholar 

  70. Abed M, Towhid ST, Shaik N, Lang F. Stimulation of suicidal death of erythrocytes by rifampicin. Toxicology. 2012;302(2–3):123–8.

    Article  CAS  PubMed  Google Scholar 

  71. Felder KM, Hoelzle K, Ritzmann M, Kilchling T, Schiele D, Heinritzi K, et al. Hemotrophic mycoplasmas induce programmed cell death in red blood cells. Cell Physiol Biochem. 2011;27:557–64.

    Article  CAS  PubMed  Google Scholar 

  72. Firat U, Kaya S, Cim A, Buyukbayram H, Gokalp O, Dal MS, et al. Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats. Exp Diabetes Res. 2012;2012:316384.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Ganesan S, Chaurasiya ND, Sahu R, Walker LA, Tekwani BL. Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway. Toxicology. 2012;294:54–60.

    Article  CAS  PubMed  Google Scholar 

  74. Gao M, Cheung KL, Lau IP, Yu WS, Fung KP, Yu B, et al. Polyphyllin D induces apoptosis in human erythrocytes through Ca(2)(+) rise and membrane permeabilization. Arch Toxicol. 2012;86:741–52.

    Article  CAS  PubMed  Google Scholar 

  75. Ghashghaeinia M, Toulany M, Saki M, Bobbala D, Fehrenbacher B, Rupec R, et al. The NFkB pathway inhibitors Bay 11-7082 and parthenolide induce programmed cell death in anucleated Erythrocytes. Cell Physiol Biochem. 2011;27:45–54.

    Article  CAS  PubMed  Google Scholar 

  76. Jilani K, Lupescu A, Zbidah M, Abed M, Shaik N, Lang F. Enhanced apoptotic death of erythrocytes induced by the mycotoxin ochratoxin A. Kidney Blood Press Res. 2012;36:107–18.

    Article  CAS  PubMed  Google Scholar 

  77. Kucherenko YV, Lang F. Inhibitory effect of furosemide on non-selective voltage-independent cation channels in human erythrocytes. Cell Physiol Biochem. 2012;30:863–75.

    Article  CAS  PubMed  Google Scholar 

  78. Qadri SM, Kucherenko Y, Lang F. Beauvericin induced erythrocyte cell membrane scrambling. Toxicology. 2011;283:24–31.

    Article  CAS  PubMed  Google Scholar 

  79. Qian EW, Ge DT, Kong SK. Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis. J Nat Prod. 2012;75:531–7.

    Article  CAS  PubMed  Google Scholar 

  80. Shaik N, Zbidah M, Lang F. Inhibition of Ca(2+) entry and suicidal erythrocyte death by naringin. Cell Physiol Biochem. 2012;30:678–86.

    Article  CAS  PubMed  Google Scholar 

  81. Vota DM, Maltaneri RE, Wenker SD, Nesse AB, Vittori DC. Differential erythropoietin action upon cells induced to eryptosis by different agents. Cell Biochem Biophys. 2013;65(2):145–57.

    Article  CAS  PubMed  Google Scholar 

  82. Weiss E, Cytlak UM, Rees DC, Osei A, Gibson JS. Deoxygenation-induced and Ca(2+) dependent phosphatidylserine externalisation in red blood cells from normal individuals and sickle cell patients. Cell Calcium. 2012;51:51–6.

    Article  CAS  PubMed  Google Scholar 

  83. Zappulla D. Environmental stress, erythrocyte dysfunctions, inflammation, and the metabolic syndrome: adaptations to CO2 increases? J Cardiometab Syndr. 2008;3:30–4.

    Article  PubMed  Google Scholar 

  84. Zbidah M, Lupescu A, Jilani K, Lang F. Stimulation of suicidal erythrocyte death by fumagillin. Basic Clin Pharmacol Toxicol. 2013;112(5):346–51.

    Article  CAS  PubMed  Google Scholar 

  85. Jilani K, Qadri SM, Lang F. Geldanamycin-induced phosphatidylserine translocation in the erythrocyte membrane. Cell Physiol Biochem. 2013;32:1600–9.

    CAS  PubMed  Google Scholar 

  86. Bissinger R, Modicano P, Frauenfeld L, Lang E, Jacobi J, Faggio C, et al. Estramustine-induced suicidal erythrocyte death. Cell Physiol Biochem. 2013;32:1426–36.

    Article  CAS  PubMed  Google Scholar 

  87. Abed M, Herrmann T, Alzoubi K, Pakladok T, Lang F. Tannic acid induced suicidal erythrocyte death. Cell Physiol Biochem. 2013;32:1106–16.

    Article  CAS  PubMed  Google Scholar 

  88. Abed M, Feger M, Alzoubi K, Pakladok T, Frauenfeld L, Geiger C, et al. Sensitization of erythrocytes to suicidal erythrocyte death following water deprivation. Kidney Blood Press Res. 2013;37:567–78.

    CAS  PubMed  Google Scholar 

  89. Ahmed MS, Langer H, Abed M, Voelkl J, Lang F. The uremic toxin acrolein promotes suicidal erythrocyte death. Kidney Blood Press Res. 2013;37:158–67.

    Article  PubMed  Google Scholar 

  90. Ghashghaeinia M, Cluitmans JC, Toulany M, Saki M, Koberle M, Lang E, et al. Age sensitivity of NFkappaB abundance and programmed cell death in erythrocytes induced by NFkappaB inhibitors. Cell Physiol Biochem. 2013;32:801–13.

    Article  CAS  PubMed  Google Scholar 

  91. Lupescu A, Jilani K, Zbidah M, Lang F. Patulin-induced suicidal erythrocyte death. Cell Physiol Biochem. 2013;32:291–9.

    Article  CAS  PubMed  Google Scholar 

  92. Calderon-Salinas JV, Munoz-Reyes EG, Guerrero-Romero JF, Rodriguez-Moran M, Bracho-Riquelme RL, Carrera-Gracia MA, et al. Eryptosis and oxidative damage in type 2 diabetic mellitus patients with chronic kidney disease. Mol Cell Biochem. 2011;357:171–9.

    Article  CAS  PubMed  Google Scholar 

  93. Nicolay JP, Schneider J, Niemoeller OM, Artunc F, Portero-Otin M, Haik G Jr, et al. Stimulation of suicidal erythrocyte death by methylglyoxal. Cell Physiol Biochem. 2006;18:223–32.

    Article  CAS  PubMed  Google Scholar 

  94. Myssina S, Huber SM, Birka C, Lang PA, Lang KS, Friedrich B, et al. Inhibition of erythrocyte cation channels by erythropoietin. J Am Soc Nephrol. 2003;14:2750–7.

    Article  CAS  PubMed  Google Scholar 

  95. Kempe DS, Akel A, Lang PA, Hermle T, Biswas R, Muresanu J, et al. Suicidal erythrocyte death in sepsis. J Mol Med. 2007;85:269–77.

    Article  Google Scholar 

  96. Foller M, Bobbala D, Koka S, Huber SM, Gulbins E, Lang F. Suicide for survival–death of infected erythrocytes as a host mechanism to survive malaria. Cell Physiol Biochem. 2009;24:133–40.

    Article  PubMed  Google Scholar 

  97. Lang PA, Kasinathan RS, Brand VB, Duranton C, Lang C, Koka S, et al. Accelerated clearance of plasmodium-infected erythrocytes in sickle cell trait and annexin-A7 deficiency. Cell Physiol Biochem. 2009;24:415–28.

    Article  CAS  PubMed  Google Scholar 

  98. Lang PA, Schenck M, Nicolay JP, Becker JU, Kempe DS, Lupescu A, et al. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat Med. 2007;13:164–70.

    Article  CAS  PubMed  Google Scholar 

  99. Kempe DS, Lang PA, Duranton C, Akel A, Lang KS, Huber SM, et al. Enhanced programmed cell death of iron-deficient erythrocytes. FASEB J. 2006;20:368–70.

    CAS  PubMed  Google Scholar 

  100. Qadri SM, Mahmud H, Lang E, Gu S, Bobbala D, Zelenak C, et al. Enhanced suicidal erythrocyte death in mice carrying a loss-of-function mutation of the adenomatous polyposis coli gene. J Cell Mol Med. 2012;16:1085–93.

    Article  CAS  PubMed  Google Scholar 

  101. Birka C, Lang PA, Kempe DS, Hoefling L, Tanneur V, Duranton C, et al. Enhanced susceptibility to erythrocyte “apoptosis” following phosphate depletion. Pflugers Arch. 2004;448:471–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the meticulous preparation of the manuscript by Tanja Loch and Ali Soleimanpour. The study was supported by the Deutsche Forschungsgemeinschaft.

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The authors declare that they have no conflict of interest.

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Correspondence to Florian Lang.

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Bissinger, R., Modicano, P., Alzoubi, K. et al. Effect of saponin on erythrocytes. Int J Hematol 100, 51–59 (2014). https://doi.org/10.1007/s12185-014-1605-z

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  • DOI: https://doi.org/10.1007/s12185-014-1605-z

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