Eryptosis is a regulated cell death (RCD) of mature erythrocytes initially described as a counterpart of apoptosis for enucleated cells. However, over the recent years, a growing number of studies have emphasized certain differences between both cell death modalities. In this review paper, we underline the hallmarks of eryptosis and apoptosis and highlight resemblances and dissimilarities between both RCDs. We summarize and critically discuss differences in the impact of caspase-3, Ca2+ signaling, ROS signaling pathways, opposing roles of casein kinase 1α, protein kinase C, Janus kinase 3, cyclin-dependent kinase 4, and AMP-activated protein kinase to highlight a certain degree of divergence between apoptosis and eryptosis. This review emphasizes the crucial importance of further studies that focus on deepening our knowledge of cell death machinery and identifying novel differences between cell death of nucleated and enucleated cells. This might provide evidence that erythrocytes can be defined as viable entities capable of programmed cell destruction. Additionally, the revealed cell type-specific patterns in cell death can facilitate the development of cell death-modulating therapeutic agents.

1st Faculty of Medicine BIOCEV Charles University Průmyslová 595 25250 Vestec Czech Republic

Zobrazit více v PubMed

Galluzzi L, Vitale I, Aaronson SA et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541 PubMed PMC

Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G (2019) The molecular machinery of regulated cell death. Cell Res 29:347–364 PubMed PMC

Cui J, Zhao S, Li Y et al (2021) Regulated cell death: discovery, features and implications for neurodegenerative diseases. Cell Commun Signal 19:120 PubMed PMC

Peng F, Liao M, Qin R et al (2022) Regulated cell death (RCD) in cancer: key pathways and targeted therapies. Signal Transduct Target Ther 7:286 PubMed PMC

Green DR, Llambi F. (2015) Cell Death Signaling. Cold Spring Harb Perspect Biol 7

Santagostino SF, Assenmacher CA, Tarrant JC, Adedeji AO, Radaelli E (2021) Mechanisms of regulated cell death: current perspectives. Vet Pathol 58:596–623 PubMed

Wu C, Zhou L, Yuan H, Wu S (2020) Interconnections among major forms of regulated cell death. Apoptosis 25:616–624 PubMed

Gullett JM, Tweedell RE, Kanneganti TD (2022) It’s all in the PAN: crosstalk, plasticity, redundancies, switches, and interconnectedness encompassed by PANoptosis underlying the totality of cell death-associated biological effects. Cells 11(9):1495 PubMed PMC

Naeini MB, Bianconi V, Pirro M, Sahebkar A (2020) The role of phosphatidylserine recognition receptors in multiple biological functions. Cell Mol Biol Lett 25:23 PubMed PMC

Galluzzi L, Kepp O, Hett E, Kroemer G, Marincola FM (2023) Immunogenic cell death in cancer: concept and therapeutic implications. J Transl Med 21:162 PubMed PMC

Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72 PubMed

Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G (2017) Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 17:97–111 PubMed

Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z (2019) Immunogenic cell death in cancer therapy: present and emerging inducers. J Cell Mol Med 23:4854–4865 PubMed PMC

Nemkov T, Reisz JA, Xia Y, Zimring JC, D’Alessandro A (2018) Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport. Expert Rev Proteom 15:855–864

Anderson HL, Brodsky IE, Mangalmurti NS (2018) The evolving erythrocyte: red blood cells as modulators of innate immunity. J Immunol 201:1343–1351 PubMed

Lam LKM, Murphy S, Kokkinaki D et al (2021) DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci Transl Med 13:eabj1008 PubMed PMC

Minton K (2021) Red blood cells join the ranks as immune sentinels. Nat Rev Immunol 21:760–761 PubMed PMC

Ren Y, Yan C, Yang H (2023) Erythrocytes: member of the immune system that should not be ignored. Crit Rev Oncol Hematol 187:104039 PubMed

Arias CF, Arias CF (2017) How do red blood cells know when to die? R Soc Open Sci 4:160850 PubMed PMC

Thiagarajan P, Parker CJ, Prchal JT (2021) How do red blood cells die? Front Physiol 12:655393 PubMed PMC

Rapido F (2017) The potential adverse effects of haemolysis. Blood Transfus 15:218–221 PubMed PMC

von Petersdorff-Campen K, Schmid DM (2022) Hemolysis testing in vitro: a review of challenges and potential improvements. Asaio J 68:3–13

Lang F, Qadri SM (2012) Mechanisms and significance of eryptosis, the suicidal death of erythrocytes. Blood Purif 33:125–130 PubMed

Pretorius E, du Plooy JN, Bester J (2016) A comprehensive review on eryptosis. Cell Physiol Biochem 39:1977–2000 PubMed

Repsold L, Joubert AM (2018) Eryptosis: an erythrocyte’s suicidal type of cell death. Biomed Res Int 2018:9405617 PubMed PMC

Dreischer P, Duszenko M, Stein J, Wieder T (2022) Eryptosis: programmed death of nucleus-free, iron-filled blood cells. Cells 11(3):503 PubMed PMC

Alghareeb SA, Alfhili MA, Fatima S (2023) Molecular mechanisms and pathophysiological significance of eryptosis. Int J Mol Sci 24(6):5079 PubMed PMC

Tkachenko A, Onishchenko A (2023) Casein kinase 1α mediates eryptosis: a review. Apoptosis 28:1–19 PubMed

LaRocca TJ, Stivison EA, Hod EA et al (2014) Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes. MBio 5:e01251-e11214 PubMed PMC

LaRocca TJ, Stivison EA, Mal-Sarkar T et al (2015) CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis. Cell Death Dis 6:e1773 PubMed PMC

LaRocca TJ, Sosunov SA, Shakerley NL, Ten VS, Ratner AJ (2016) Hyperglycemic conditions prime cells for RIP1-dependent necroptosis. J Biol Chem 291:13753–13761 PubMed PMC

McCaig WD, Hodges AL, Deragon MA et al (2019) Storage primes erythrocytes for necroptosis and clearance. Cell Physiol Biochem 53:496–507 PubMed

Seo J, Kim Y, Ji S et al (2023) O-GlcNAcylation of RIPK1 rescues red blood cells from necroptosis. Front Immunol 14:1160490 PubMed PMC

Gao W, Wang X, Zhou Y, Wang X, Yu Y (2022) Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct Target Ther 7:196 PubMed PMC

Chang CF, Goods BA, Askenase MH et al (2018) Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage. J Clin Invest 128:607–624 PubMed

Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257 PubMed PMC

Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:528–537 PubMed

Doonan F, Cotter TG (2008) Morphological assessment of apoptosis. Methods 44:200–204 PubMed

Lang F, Lang KS, Lang PA, Huber SM, Wieder T (2006) Mechanisms and significance of eryptosis. Antioxid Redox Signal 8:1183–1192 PubMed

Aoki K, Satoi S, Harada S, Uchida S, Iwasa Y, Ikenouchi J (2020) Coordinated changes in cell membrane and cytoplasm during maturation of apoptotic bleb. Mol Biol Cell 31:833–844 PubMed PMC

Larsen AK, Lametsch R, Elce J et al (2008) Genetic disruption of calpain correlates with loss of membrane blebbing and differential expression of RhoGDI-1, cofilin and tropomyosin. Biochem J 411:657–666 PubMed

Föller M, Lang F (2020) Ion transport in eryptosis, the suicidal death of erythrocytes. Front Cell Dev Biol 8:597 PubMed PMC

Bortner CD, Cidlowski JA (2007) Cell shrinkage and monovalent cation fluxes: role in apoptosis. Arch Biochem Biophys 462:176–188 PubMed PMC

Bortner CD, Cidlowski JA (2003) Uncoupling cell shrinkage from apoptosis reveals that Na+ influx is required for volume loss during programmed cell death. J Biol Chem 278:39176–39184 PubMed

Wang XQ, Xiao AY, Sheline C et al (2003) Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. J Cell Sci 116:2099–2110 PubMed

Bortner CD, Cidlowski JA (2014) Ion channels and apoptosis in cancer. Philos Trans R Soc Lond B Biol Sci 369:20130104 PubMed PMC

Bortner CD, Cidlowski JA (2020) Ions, the movement of water and the apoptotic volume decrease. Front Cell Dev Biol 8:611211 PubMed PMC

von Lindern M, Egée S, Bianchi P, Kaestner L (2022) The function of ion channels and membrane potential in red blood cells: toward a systematic analysis of the erythroid channelome. Front Physiol 13:824478

Sakuragi T, Nagata S (2023) Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases. Nat Rev Mol Cell Biol 24:576–596 PubMed

Segawa K, Nagata S (2015) An apoptotic “eat me” signal: phosphatidylserine exposure. Trends Cell Biol 25:639–650 PubMed

Shlomovitz I, Speir M, Gerlic M (2019) Flipping the dogma - phosphatidylserine in non-apoptotic cell death. Cell Commun Signal 17:139 PubMed PMC

Calianese DC, Birge RB (2020) Biology of phosphatidylserine (PS): basic physiology and implications in immunology, infectious disease, and cancer. Cell Commun Sig 18:41

Lang PA, Kempe DS, Myssina S et al (2005) PGE2 in the regulation of programmed erythrocyte death. Cell Death Differ 12:415–428 PubMed

Lang F, Gulbins E, Lang PA, Zappulla D, Föller M (2010) Ceramide in suicidal death of erythrocytes. Cell Physiol Biochem 26:21–28 PubMed

Mullen TD, Obeid LM (2012) Ceramide and apoptosis: exploring the enigmatic connections between sphingolipid metabolism and programmed cell death. Anticancer Agents Med Chem 12:340–363 PubMed

Lang E, Bissinger R, Gulbins E, Lang F (2015) Ceramide in the regulation of eryptosis, the suicidal erythrocyte death. Apoptosis 20:758–767 PubMed

Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 1863:2977–2992 PubMed

Bissinger R, Bhuyan AAM, Qadri SM, Lang F (2019) Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases. Febs j 286:826–854 PubMed

Kagan T, Stoyanova G, Lockshin RA, Zakeri Z (2022) Ceramide from sphingomyelin hydrolysis induces neuronal differentiation, whereas de novo ceramide synthesis and sphingomyelin hydrolysis initiate apoptosis after NGF withdrawal in PC12 Cells. Cell Commun Sig 20:15

Jeffries KA, Krupenko NI (2018) Ceramide signaling and p53 pathways. Adv Cancer Res 140:191–215 PubMed PMC

Hage-Sleiman R, Esmerian MO, Kobeissy H, Dbaibo G (2013) p53 and ceramide as collaborators in the stress response. Int J Mol Sci 14:4982–5012 PubMed PMC

Dumitru CA, Gulbins E (2006) TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis. Oncogene 25:5612–5625 PubMed

Zhang T, Barclay L, Walensky LD, Saghatelian A (2015) Regulation of mitochondrial ceramide distribution by members of the BCL-2 family. J Lipid Res 56:1501–1510 PubMed PMC

Lalier L, Pedelaborde F, Braud C, Menanteau J, Vallette MF, Olivier C (2011) Increase in intracellular PGE2 induces apoptosis in bax-expressing colon cancer cell. BMC Cancer 11:153 PubMed PMC

Kovarova M, Koller BH (2014) PGE PubMed PMC

Maher TM, Evans IC, Bottoms SE et al (2010) Diminished prostaglandin E2 contributes to the apoptosis paradox in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 182:73–82 PubMed PMC

Huang SK, White ES, Wettlaufer SH et al (2009) Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways. Faseb J 23:4317–4326 PubMed PMC

Porter RL, Georger MA, Calvi LM (2011) Prostaglandin E2 inhibits apoptosis in hematopoietic stem and progenitor cells and enhances their survival following sub-lethal radiation injury. Blood 118:3401

Porter RL, Georger MA, Bromberg O et al (2013) Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury. Stem Cells 31:372–383 PubMed

Tesoriere L, Attanzio A, Allegra M, Livrea MA (2015) Dietary indicaxanthin from cactus pear (Opuntia ficus-indica L. Mill) fruit prevents eryptosis induced by oxysterols in a hypercholesterolaemia-relevant proportion and adhesion of human erythrocytes to endothelial cell layers. Br J Nutr 114:368–375 PubMed

Kazanietz MG, Caloca MJ (2017) The rac GTPase in cancer: from old concepts to new paradigms. Cancer Res 77:5445–5451 PubMed PMC

Lee CF, Carley RE, Butler CA, Morrison AR (2021) Rac GTPase signaling in immune-mediated mechanisms of atherosclerosis. Cells 10:2808 PubMed PMC

Embade N, Valerón PF, Aznar S, López-Collazo E, Lacal JC (2000) Apoptosis induced by Rac GTPase correlates with induction of FasL and ceramides production. Mol Biol Cell 11:4347–4358 PubMed PMC

Jin S, Ray RM, Johnson LR (2006) Rac1 mediates intestinal epithelial cell apoptosis via JNK. Am J Physiol Gastrointest Liver Physiol 291:G1137–G1147 PubMed

Coleman ML, Olson MF (2002) Rho GTPase signalling pathways in the morphological changes associated with apoptosis. Cell Death Differ 9:493–504 PubMed

Zhang B, Zhang Y, Shacter E (2003) Caspase 3-mediated inactivation of rac GTPases promotes drug-induced apoptosis in human lymphoma cells. Mol Cell Biol 23:5716–5725 PubMed PMC

Stankiewicz TR, Ramaswami SA, Bouchard RJ, Aktories K, Linseman DA (2015) Neuronal apoptosis induced by selective inhibition of Rac GTPase versus global suppression of Rho family GTPases is mediated by alterations in distinct mitogen-activated protein kinase signaling cascades. J Biol Chem 290:9363–9376 PubMed PMC

Paone S, D’Alessandro S, Parapini S et al (2020) Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion. Sci Rep 10:22054 PubMed PMC

Kalfa TA, Pushkaran S, Mohandas N et al (2006) Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton. Blood 108:3637–3645 PubMed PMC

Konstantinidis DG, George A, Kalfa TA (2010) Rac GTPases in erythroid biology. Transfus Clin Biol 17:126–130 PubMed PMC

Alghareeb SA, Alsughayyir J, Alfhili MA (2023) Stimulation of hemolysis and eryptosis by α-Mangostin through Rac1 GTPase and oxidative injury in human red blood cells. Molecules 28(18):6495 PubMed PMC

Attanzio A, Frazzitta A, Cilla A, Livrea MA, Tesoriere L, Allegra M (2019) 7-Keto-cholesterol and cholestan-3beta, 5alpha, 6beta-Triol induce eryptosis through distinct pathways leading to NADPH oxidase and nitric oxide synthase activation. Cell Physiol Biochem 53:933–947 PubMed

George A, Pushkaran S, Konstantinidis DG et al (2013) Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood 121:2099–2107 PubMed PMC

Lundberg JO, Weitzberg E (2022) Nitric oxide signaling in health and disease. Cell 185:2853–2878 PubMed

Kim PK, Zamora R, Petrosko P, Billiar TR (2001) The regulatory role of nitric oxide in apoptosis. Int Immunopharmacol 1:1421–1441 PubMed

Chanvorachote P, Nimmannit U, Wang L et al (2005) Nitric oxide negatively regulates fas CD95-induced apoptosis through inhibition of ubiquitin-proteasome-mediated degradation of FLICE inhibitory protein*. J Biol Chem 280:42044–42050 PubMed

Brüne B (2003) Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ 10:864–869 PubMed

Snyder CM, Shroff EH, Liu J, Chandel NS (2009) Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family members. PLoS ONE 4:e7059 PubMed PMC

Nicolay JP, Liebig G, Niemoeller OM et al (2008) Inhibition of suicidal erythrocyte death by nitric oxide. Pflugers Arch 456:293–305 PubMed

Matarrese P, Straface E, Pietraforte D et al (2005) Peroxynitrite induces senescence and apoptosis of red blood cells through the activation of aspartyl and cysteinyl proteases. Faseb j 19:416–418 PubMed

Doctor A, Stamler JS (2011) Nitric oxide transport in blood: a third gas in the respiratory cycle. Compr Physiol 1:541–568 PubMed

Restivo I, Attanzio A, Giardina IC, Di Gaudio F, Tesoriere L, Allegra M (2022) Cigarette smoke extract induces p38 MAPK-initiated, fas-mediated eryptosis. Int J Mol Sci 23(23):14730 PubMed PMC

Restivo I, Attanzio A, Tesoriere L, Allegra M, Garcia-Llatas G, Cilla A (2023) A mixture of dietary plant sterols at nutritional relevant serum concentration inhibits extrinsic pathway of eryptosis induced by cigarette smoke extract. Int J Mol Sci 24:1264 PubMed PMC

Sahoo G, Samal D, Khandayataray P, Murthy MK (2023) A review on caspases: key regulators of biological activities and apoptosis. Mol Neurobiol 60(10):5805–5837 PubMed

Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326(Pt 1):1–16 PubMed PMC

Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99–104 PubMed

Anson F, Thayumanavan S, Hardy JA (2021) Exogenous introduction of initiator and executioner caspases results in different apoptotic outcomes. JACS Au 1:1240–1256 PubMed PMC

Molnár T, Pallagi P, Tél B et al (2021) Caspase-9 acts as a regulator of necroptotic cell death. Febs j 288:6476–6491 PubMed

Dhuriya YK, Sharma D (2018) Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflamm 15:199

Fritsch M, Günther SD, Schwarzer R et al (2019) Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature 575:683–687 PubMed

Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X (2021) Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther 6:128 PubMed PMC

Song Y, Song J, Wang M, Wang J, Ma B, Zhang W (2022) Porcine gasdermin D is a substrate of caspase-1 and an executioner of pyroptosis. Front Immunol 13:828911 PubMed PMC

Tsuchiya K, Nakajima S, Hosojima S et al (2019) Caspase-1 initiates apoptosis in the absence of gasdermin D. Nat Commun 10:2091 PubMed PMC

Tsapras P, Nezis IP (2017) Caspase involvement in autophagy. Cell Death Differ 24:1369–1379 PubMed PMC

Eskandari E, Eaves CJ (2022) Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J Cell Biol 221(6):e202201159 PubMed PMC

Boland K, Flanagan L, Prehn JH (2013) Paracrine control of tissue regeneration and cell proliferation by Caspase-3. Cell Death Dis 4:e725 PubMed PMC

Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH (2013) Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol 14:32 PubMed PMC

Al-Aamri HM, Irving HR, Bradley C, Meehan-Andrews T (2021) Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment. BMC Cancer 21:438 PubMed PMC

Bai X, Kinney WH, Su WL et al (2015) Caspase-3-independent apoptotic pathways contribute to interleukin-32γ-mediated control of Mycobacterium tuberculosis infection in THP-1 cells. BMC Microbiol 15:39 PubMed PMC

Zhang L, Yan J, Liu Y et al (2017) Contribution of caspase-independent pathway to apoptosis in malignant glioma induced by carbon ion beams. Oncol Rep 37:2994–3000 PubMed

Crowley LC, Waterhouse NJ (2016) Detecting cleaved caspase-3 in apoptotic cells by flow cytometry. Cold Spring Harb Protoc. https://doi.org/10.1101/pdb.prot087312 PubMed DOI

Suzuki Y, Ohkubo N, Aoto M et al (2007) Participation of caspase-3-like protease in oxidation-induced impairment of erythrocyte membrane properties. Biorheology 44:179–190 PubMed

Rinalducci S, Ferru E, Blasi B, Turrini F, Zolla L (2012) Oxidative stress and caspase-mediated fragmentation of cytoplasmic domain of erythrocyte band 3 during blood storage. Blood Transfus 10(Suppl 2):s55-62 PubMed PMC

Qian EW, Ge DT, Kong SK (2012) Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis. J Nat Prod 75:531–537 PubMed

Maellaro E, Leoncini S, Moretti D et al (2013) Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients. Acta Diabetol 50:489–495 PubMed

Chan WY, Lau PM, Yeung KW, Kong SK (2018) The second generation tyrosine kinase inhibitor dasatinib induced eryptosis in human erythrocytes-An in vitro study. Toxicol Lett 295:10–21 PubMed

Jarosiewicz M, Michałowicz J, Bukowska B (2019) In vitro assessment of eryptotic potential of tetrabromobisphenol A and other bromophenolic flame retardants. Chemosphere 215:404–412 PubMed

Yeung KW, Lau PM, Tsang HL, Ho HP, Kwan YW, Kong SK (2019) Extracellular histones induced eryptotic death in human erythrocytes. Cell Physiol Biochem 53:229–241 PubMed

Chen Z, Yang B, Yan Z, Song E, Song Y (2022) Eryptosis is an indicator of hematotoxicity in the risk assessment of environmental amorphous silica nanoparticles exposure: the role of macromolecule corona. Toxicol Lett 367:40–47 PubMed

Lupescu A, Shaik N, Jilani K et al (2012) Enhanced erythrocyte membrane exposure of phosphatidylserine following sorafenib treatment: an in vivo and in vitro study. Cell Physiol Biochem 30:876–888 PubMed

Al Mamun Bhuyan A, Bissinger R, Cao H, Lang F (2016) Triggering of suicidal erythrocyte death by bexarotene. Cell Physiol Biochem 40:1239–1251 PubMed

Al Mamun Bhuyan A, Signoretto E, Bissinger R, Lang F (2016) Enhanced eryptosis following exposure to dolutegravir. Cell Physiol Biochem 39:639–650 PubMed

Al Mamun Bhuyan A, Bissinger R, Stockinger K, Lang F (2016) Stimulation of suicidal erythrocyte death by tafenoquine. Cell Physiol Biochem 39:2464–2476 PubMed

Jemaà M, Mischitelli M, Fezai M, Almasry M, Faggio C, Lang F (2016) Stimulation of suicidal erythrocyte death by the CDC25 inhibitor NSC-95397. Cell Physiol Biochem 40:597–607 PubMed

Signoretto E, Honisch S, Briglia M, Faggio C, Castagna M, Lang F (2016) Nocodazole induced suicidal death of human erythrocytes. Cell Physiol Biochem 38:379–392 PubMed

Al Mamun Bhuyan A, Bissinger R, Cao H, Lang F (2017) Triggering of suicidal erythrocyte death by exemestane. Cell Physiol Biochem 42:1–12 PubMed

Ferdous Z, Beegam S, Tariq S, Ali BH, Nemmar A (2018) The in vitro effect of polyvinylpyrrolidone and citrate coated silver nanoparticles on erythrocytic oxidative damage and eryptosis. Cell Physiol Biochem 49:1577–1588 PubMed

Alfhili MA, Aljuraiban GS (2021) Lauric acid, a dietary saturated medium-chain fatty acid Elicits calcium-dependent eryptosis. Cells 10:3388 PubMed PMC

Alfhili MA, Basudan AM, Aljaser FS, Dera A, Alsughayyir J (2021) Bioymifi, a novel mimetic of TNF-related apoptosis-induced ligand (TRAIL), stimulates eryptosis. Med Oncol 38:138 PubMed

Allegra M, Restivo I, Fucarino A et al (2020) Proeryptotic activity of 4-hydroxynonenal: a new potential physiopathological role for lipid peroxidation products. Biomolecules 10(5):770 PubMed PMC

Jin Q, Yao C, Bian Y, Pi J (2022) Pb-induced eryptosis may provoke thrombosis prior to hemolysis. Int J Mol Sci 23:7008 PubMed PMC

Mandal D, Moitra PK, Saha S, Basu J (2002) Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes. FEBS Lett 513:184–188 PubMed

Wang J, Zhen L, Klug MG, Wood D, Wu X, Mizrahi J (2000) Involvement of caspase 3- and 8-like proteases in ceramide-induced apoptosis of cardiomyocytes. J Card Fail 6:243–249 PubMed

Ravid T, Tsaba A, Gee P, Rasooly R, Medina EA, Goldkorn T (2003) Ceramide accumulation precedes caspase-3 activation during apoptosis of A549 human lung adenocarcinoma cells. Am J Physiol Lung Cell Mol Physiol 284:L1082-1092 PubMed

Bhavsar SK, Bobbala D, Xuan NT, Föller M, Lang F (2010) Stimulation of suicidal erythrocyte death by α-lipoic acid. Cell Physiol Biochem 26:859–868 PubMed

Abed M, Thiel C, Towhid ST et al (2017) Stimulation of erythrocyte cell membrane scrambling by C-reactive protein. Cell Physiol Biochem 41:806–818 PubMed

Bissinger R, Malik A, Honisch S, Warsi J, Jilani K, Lang F (2014) In vitro sensitization of erythrocytes to programmed cell death following baicalein treatment. Toxins (Basel) 6:2771–2786 PubMed

Bissinger R, Bouguerra G, Stockinger K, Abbès S, Lang F (2015) Triggering of suicidal erythrocyte death by topotecan. Cell Physiol Biochem 37:1607–1618 PubMed

Faggio C, Alzoubi K, Calabrò S, Lang F (2015) Stimulation of suicidal erythrocyte death by PRIMA-1. Cell Physiol Biochem 35:529–540 PubMed

Al Mamun Bhuyan A, Cao H, Lang F (2017) Triggering of eryptosis, the suicidal erythrocyte death by mammalian target of rapamycin (mTOR) inhibitor temsirolimus. Cell Physiol Biochem 42:1575–1591 PubMed

Zhu J, Jin M, Wang J et al (2018) TNFα induces Ca2+ influx to accelerate extrinsic apoptosis in hepatocellular carcinoma cells. J Exp Clin Cancer Res 37:43 PubMed PMC

Pedrera L, Espiritu RA, Ros U et al (2021) Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics. Cell Death Differ 28:1644–1657 PubMed

Danese A, Leo S, Rimessi A et al (2021) Cell death as a result of calcium signaling modulation: a cancer-centric prospective. Biochimica et Biophys Acta (BBA) Mol Cell Res 1868:119061

Sukumaran P, Nascimento Da Conceicao V, Sun Y et al (2021) Calcium signaling regulates autophagy and apoptosis. Cells 10(8):2125 PubMed PMC

Zheng Z, Wang T, Chen J et al (2021) Inflammasome-induced osmotic pressure and the mechanical mechanisms underlying astrocytic swelling and membrane blebbing in pyroptosis. Front Immunol 12:688674 PubMed PMC

Raffaello A, Mammucari C, Gherardi G, Rizzuto R (2016) Calcium at the center of cell signaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci 41:1035–1049 PubMed PMC

Patergnani S, Danese A, Bouhamida E et al (2020) Various aspects of calcium signaling in the regulation of apoptosis, autophagy, cell proliferation, and cancer. Int J Mol Sci 21:8323 PubMed PMC

Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R (2008) Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 27:6407–6418 PubMed PMC

Danese A, Patergnani S, Bonora M et al (2017) Calcium regulates cell death in cancer: Roles of the mitochondria and mitochondria-associated membranes (MAMs). Biochimica et Biophysica Acta BBA Bioenerg 1858:615–627

Giorgi C, Baldassari F, Bononi A et al (2012) Mitochondrial Ca(2+) and apoptosis. Cell Calcium 52:36–43 PubMed PMC

Calvo-Rodriguez M, Hou SS, Snyder AC et al (2020) Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer’s disease. Nat Commun 11:2146 PubMed PMC

Bernardi P, Gerle C, Halestrap AP et al (2023) Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell Death Differ 30:1869–1885 PubMed PMC

Waseem M, Wang B-D (2023) Promising strategy of mPTP modulation in cancer therapy: an emerging progress and future insight. Int J Mol Sci 24:5564 PubMed PMC

Matuz-Mares D, González-Andrade M, Araiza-Villanueva MG, Vilchis-Landeros MM, Vázquez-Meza H (2022) Mitochondrial calcium: effects of its imbalance in disease. Antioxidants 11:801 PubMed PMC

Görlach A, Bertram K, Hudecova S, Krizanova O (2015) Calcium and ROS: a mutual interplay. Redox Biol 6:260–271 PubMed PMC

Pinton P, Ferrari D, Magalhães P et al (2000) Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells. J Cell Biol 148:857–862 PubMed PMC

Morris JL, Gillet G, Prudent J, Popgeorgiev N (2021) Bcl-2 family of proteins in the control of mitochondrial calcium signalling: an old chap with new roles. Int J Mol Sci 22:3730 PubMed PMC

Naumova N, Šachl R (2020) Regulation of cell death by mitochondrial transport systems of calcium and Bcl-2 proteins. Membranes 10:299 PubMed PMC

Liu SI, Huang CC, Huang CJ et al (2007) Thimerosal-induced apoptosis in human SCM1 gastric cancer cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. Toxicol Sci 100:109–117 PubMed

Säll J, Carlsson M, Gidlöf O et al (2013) The antimicrobial peptide LL-37 alters human osteoblast Ca2+ handling and induces Ca2+-independent apoptosis. J Innate Immun 5:290–300 PubMed PMC

Li J, Yu Z, Wang Q et al (2014) Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway. BMC Gastroenterol 14:151 PubMed PMC

Bogdanova A, Makhro A, Wang J, Lipp P, Kaestner L (2013) Calcium in red blood cells-a perilous balance. Int J Mol Sci 14:9848–9872 PubMed PMC

Klei TRL, Dalimot JJ, Beuger BM et al (2020) The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation. Blood Adv 4:6218–6229 PubMed PMC

Bernhardt I, Nguyen DB, Wesseling MC, Kaestner L (2019) Intracellular Ca(2+) concentration and phosphatidylserine exposure in healthy human erythrocytes in dependence on in vivo cell age. Front Physiol 10:1629 PubMed

Qadri SM, Donkor DA, Bhakta V et al (2016) Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin. J Cell Mol Med 20:710–720 PubMed PMC

Gatidis S, Zelenak C, Fajol A et al (2011) p38 MAPK activation and function following osmotic shock of erythrocytes. Cell Physiol Biochem 28:1279–1286 PubMed

Zhang Y, Xu Y, Zhang S, Lu Z, Li Y, Zhao B (2022) The regulation roles of Ca(2+) in erythropoiesis: What have we learned? Exp Hematol 106:19–30 PubMed

Al Mamun Bhuyan A, Signoretto E, Lang F (2016) Triggering of suicidal erythrocyte death by psammaplin a. Cell Physiol Biochem 39:908–918 PubMed

Signoretto E, Laufer SA, Lang F (2016) Stimulating effect of sclareol on suicidal death of human erythrocytes. Cell Physiol Biochem 39:554–564 PubMed

Pan X, Giustarini D, Lang F et al (2023) Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion. Cell Cycle 22:1–27

Zhang J, Wang X, Vikash V et al (2016) ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev 2016:4350965 PubMed PMC

Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13 PubMed

Gwozdzinski K, Pieniazek A, Gwozdzinski L (2021) Reactive oxygen species and their involvement in red blood cell damage in chronic kidney disease. Oxid Med Cell Longev 2021:6639199 PubMed PMC

Fujii J, Homma T, Kobayashi S, Warang P, Madkaikar M, Mukherjee MB (2021) Erythrocytes as a preferential target of oxidative stress in blood. Free Radical Res 55:781–799

Wang Y, Shi P, Chen Q et al (2019) Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation. J Mol Cell Biol 11:1069–1082 PubMed PMC

Villalpando-Rodriguez GE, Gibson SB (2021) Reactive oxygen species (ROS) regulates different types of cell death by acting as a rheostat. Oxid Med Cell Longev 2021:9912436 PubMed PMC

Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950 PubMed PMC

Jagadish S, Hemshekhar M, NaveenKumar SK et al (2017) Novel oxolane derivative DMTD mitigates high glucose-induced erythrocyte apoptosis by regulating oxidative stress. Toxicol Appl Pharmacol 334:167–179 PubMed

Rana RB, Jilani K, Shahid M et al (2019) Atorvastatin induced erythrocytes membrane blebbing. Dose Response 17:1559325819869076 PubMed PMC

Cuevas-González PF, Aguilar-Toalá JE, García HS, González-Córdova AF, Vallejo-Cordoba B, Hernández-Mendoza A (2020) Protective effect of the intracellular content from potential probiotic bacteria against oxidative damage induced by acrylamide in human erythrocytes. Probiotics Antimicrob Proteins 12:1459–1470 PubMed

Ilyas S, Jilani K, Sikandar M et al (2020) Stimulation of erythrocyte membrane blebbing by naproxen sodium. Dose Response 18:1559325819899259 PubMed PMC

Naveed A, Jilani K, Siddique AB et al (2020) Induction of erythrocyte shrinkage by omeprazole. Dose Response 18:1559325820946941 PubMed PMC

Zangeneh AR, Takhshid MA, Ranjbaran R, Maleknia M, Meshkibaf MH (2021) Diverse effect of vitamin C and N-acetylcysteine on aluminum-induced eryptosis. Biochem Res Int 2021:6670656 PubMed PMC

Mukhtar F, Jilani K, Bibi I, Mushataq Z, Bari Khan MA, Fatima M (2022) Stimulation of erythrocyte membrane blebbing by bifenthrin induced oxidative stress. Dose Response 20:15593258221076710 PubMed PMC

Tkachenko A, Virych P, Myasoyedov V et al (2022) Cytotoxicity of hybrid noble metal-polymer composites. Biomed Res Int 2022:1487024 PubMed PMC

Duranton C, Huber SM, Lang F (2002) Oxidation induces a Cl(-)-dependent cation conductance in human red blood cells. J Physiol 539:847–855 PubMed PMC

Huber SM, Uhlemann AC, Gamper NL, Duranton C, Kremsner PG, Lang F (2002) Plasmodium falciparum activates endogenous Cl(-) channels of human erythrocytes by membrane oxidation. Embo j 21:22–30 PubMed PMC

Briglia M, Fazio A, Faggio C, Lang F (2015) Triggering of suicidal erythrocyte death by zosuquidar. Cell Physiol Biochem 37:2355–2365 PubMed

Briglia M, Fazio A, Faggio C, Laufer S, Alzoubi K, Lang F (2015) Triggering of suicidal erythrocyte death by ruxolitinib. Cell Physiol Biochem 37:768–778 PubMed

Briglia M, Fazio A, Signoretto E, Faggio C, Lang F (2015) Edelfosine induced suicidal death of human erythrocytes. Cell Physiol Biochem 37:2221–2230 PubMed

Calabrò S, Alzoubi K, Faggio C, Laufer S, Lang F (2015) Triggering of suicidal erythrocyte death following boswellic acid exposure. Cell Physiol Biochem 37:131–142 PubMed

Zierle J, Bissinger R, Egler J, Lang F (2015) Lapatinib induced suicidal death of human erythrocytes. Cell Physiol Biochem 37:2275–2287 PubMed

Peter T, Bissinger R, Lang F (2016) Stimulation of eryptosis by caspofungin. Cell Physiol Biochem 39:939–949 PubMed

Signoretto E, Bissinger R, Castagna M, Lang F (2016) Stimulation of eryptosis by combretastatin A4 phosphate disodium (CA4P). Cell Physiol Biochem 38:969–981 PubMed

Almasry M, Jemaà M, Mischitelli M, Lang F, Faggio C (2017) Camalexin-induced cell membrane scrambling and cell shrinkage in human erythrocytes. Cell Physiol Biochem 41:731–741 PubMed

Fink M, Bhuyan AAM, Nürnberg B, Faggio C, Lang F (2019) Triggering of eryptosis, the suicidal erythrocyte death, by phenoxodiol. Naunyn Schmiedebergs Arch Pharmacol 392:1311–1318 PubMed

Akiel M, Alsughayyir J, Basudan AM et al (2021) Physcion induces hemolysis and premature phosphatidylserine externalization in human erythrocytes. Biol Pharm Bull 44:372–378 PubMed

Yefimova S, Onishchenko A, Klochkov V et al (2023) Rare-earth orthovanadate nanoparticles trigger Ca2+-dependent eryptosis. Nanotechnology 34(20):205101

Stockinger K, Bissinger R, Bouguerra G, Abbès S, Lang F (2015) Enhanced eryptosis following exposure to carnosic acid. Cell Physiol Biochem 37:1779–1791 PubMed

Peter T, Bissinger R, Liu G, Lang F (2016) Anidulafungin-induced suicidal erythrocyte death. Cell Physiol Biochem 38:2272–2284 PubMed

Peter T, Bissinger R, Signoretto E, Mack AF, Lang F (2016) Micafungin-induced suicidal erythrocyte death. Cell Physiol Biochem 39:584–595 PubMed

Zhang Z, Tai Y, Liu Z et al (2023) Effects of d-ribose on human erythrocytes: non-enzymatic glycation of hemoglobin, eryptosis, oxidative stress and energy metabolism. Blood Cells Mol Dis 99:102725 PubMed

Lau IP, Chen H, Wang J et al (2012) In vitro effect of CTAB- and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology 6:847–856 PubMed

Officioso A, Alzoubi K, Lang F, Manna C (2016) Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: possible involvement of the glutathione pathway. Food Chem Toxicol 89:47–53 PubMed

Qadri SM, Chen D, Schubert P et al (2017) Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis. Transfusion 57:661–673 PubMed

Dias GF, Bonan NB, Steiner TM et al (2018) Indoxyl sulfate, a uremic toxin, stimulates reactive oxygen species production and erythrocyte cell death supposedly by an organic anion transporter 2 (OAT2) and NADPH oxidase activity-dependent pathways. Toxins (Basel) 10(7):280 PubMed

Bukowska B (2021) Changes in human erythrocyte exposed to organophosphate flame retardants: Tris(2-chloroethyl) phosphate and Tris(1-chloro-2-propyl) phosphate. Materials (Basel) 14(13):3675 PubMed

Zhang Y, Chen X, Gueydan C, Han J (2018) Plasma membrane changes during programmed cell deaths. Cell Res 28:9–21 PubMed

Qadri SM, Bissinger R, Solh Z, Oldenborg PA (2017) Eryptosis in health and disease: a paradigm shift towards understanding the (patho)physiological implications of programmed cell death of erythrocytes. Blood Rev 31:349–361 PubMed

Ewendt F, Schmitt M, Kluttig A et al (2023) Association between vitamin D status and eryptosis–results from the German National Cohort Study. Ann Hematol 102:1351–1361 PubMed PMC

Pyrshev KA, Klymchenko AS, Csúcs G, Demchenko AP (2018) Apoptosis and eryptosis: striking differences on biomembrane level. Biochimica et Biophysica Acta (BBA) Biomembr 1860:1362–1371

Jourd’heuil D, Aspinall A, Reynolds JD, Meddings JB (1996) Membrane fluidity increases during apoptosis of sheep ileal Peyer’s patch B cells. Can J Physiol Pharmacol 74:706–711 PubMed

Fujimoto K, Iwasaki C, Kawaguchi H, Yasugi E, Oshima M (1999) Cell membrane dynamics and the induction of apoptosis by lipid compounds. FEBS Lett 446:113–116 PubMed

Raghavendra PB, Sreenivasan Y, Manna SK (2007) Oleandrin induces apoptosis in human, but not in murine cells: dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity. Mol Immunol 44:2292–2302 PubMed

Oncul S, Klymchenko AS, Kucherak OA et al (2010) Liquid ordered phase in cell membranes evidenced by a hydration-sensitive probe: effects of cholesterol depletion and apoptosis. Biochim Biophys Acta 1798:1436–1443 PubMed

Darwich Z, Klymchenko AS, Kucherak OA, Richert L, Mély Y (2012) Detection of apoptosis through the lipid order of the outer plasma membrane leaflet. Biochimica et Biophysica Acta (BBA) Biomembr 1818:3048–3054

Pyrshev KA, Yesylevskyy SO, Mély Y, Demchenko AP, Klymchenko AS (2017) Caspase-3 activation decreases lipid order in the outer plasma membrane leaflet during apoptosis: a fluorescent probe study. Biochim Biophys Acta Biomembr 1859:2123–2132 PubMed

Gibbons E, Pickett KR, Streeter MC et al (2013) Molecular details of membrane fluidity changes during apoptosis and relationship to phospholipase A(2) activity. Biochim Biophys Acta 1828:887–895 PubMed

Bailey RW, Nguyen T, Robertson L et al (2009) Sequence of physical changes to the cell membrane during glucocorticoid-induced apoptosis in S49 lymphoma cells. Biophys J 96:2709–2718 PubMed PMC

Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM (2000) Serine/threonine protein kinases and apoptosis. Exp Cell Res 256:34–41 PubMed

Franklin RA, McCubrey JA (2000) Kinases: positive and negative regulators of apoptosis. Leukemia 14:2019–2034 PubMed

Jiang S, Zhang M, Sun J, Yang X (2018) Casein kinase 1α: biological mechanisms and theranostic potential. Cell Commun Sig 16:23

Sinnberg T, Menzel M, Kaesler S et al (2010) Suppression of casein kinase 1alpha in melanoma cells induces a switch in beta-catenin signaling to promote metastasis. Cancer Res 70:6999–7009 PubMed

Sinnberg T, Wang J, Sauer B, Schittek B (2016) Casein kinase 1α has a non-redundant and dominant role within the CK1 family in melanoma progression. BMC Cancer 16:594 PubMed PMC

Desagher S, Osen-Sand A, Montessuit S et al (2001) Phosphorylation of bid by casein kinases I and II regulates its cleavage by caspase 8. Mol Cell 8:601–611 PubMed

Zhao Y, Qin S, Atangan LI et al (2004) Casein Kinase 1α Interacts with Retinoid X Receptor and Interferes with Agonist-induced Apoptosis*. J Biol Chem 279:30844–30849 PubMed

Zheng J, Kong C, Yang X, Cui X, Lin X, Zhang Z (2017) Protein kinase C-α (PKCα) modulates cell apoptosis by stimulating nuclear translocation of NF-kappa-B p65 in urothelial cell carcinoma of the bladder. BMC Cancer 17:432 PubMed PMC

Xu W, Huang Z, Gan Y et al (2020) Casein kinase 1α inhibits p53 downstream of MDM2-mediated autophagy and apoptosis in acute myeloid leukemia. Oncol Rep 44:1895–1904 PubMed PMC

Behrouj H, Seghatoleslam A, Mokarram P, Ghavami S (2021) Effect of casein kinase 1α inhibition on autophagy flux and the AKT/phospho-β-catenin (S552) axis in HCT116, a RAS-mutated colorectal cancer cell line. Can J Physiol Pharmacol 99:284–293 PubMed

Zelenak C, Eberhard M, Jilani K, Qadri SM, Macek B, Lang F (2012) Protein kinase CK1α regulates erythrocyte survival. Cell Physiol Biochem 29:171–180 PubMed

Parker PJ, Brown SJ, Calleja V et al (2021) Equivocal, explicit and emergent actions of PKC isoforms in cancer. Nat Rev Cancer 21:51–63 PubMed

Reyland ME (2007) Protein Kinase C and Apoptosis. In: Srivastava R (ed) Apoptosis, Cell Signaling, and Human Diseases: Molecular Mechanisms, vol 2. Humana Press. Totowa, pp 31–55

Zhu T, Tsuji T, Chen C (2010) Roles of PKC isoforms in the induction of apoptosis elicited by aberrant Ras. Oncogene 29:1050–1061 PubMed

Bluwstein A, Kumar N, Léger K et al (2013) PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts. Cell Death Dis 4:e498–e498 PubMed PMC

Singh RK, Kumar S, Gautam PK et al (2017) Protein kinase C-α and the regulation of diverse cell responses. Biomol Concepts 8:143–153 PubMed

Ghashghaeinia M, Koralkova P, Giustarini D et al (2020) The specific PKC-α inhibitor chelerythrine blunts costunolide-induced eryptosis. Apoptosis 25:674–685 PubMed PMC

Klarl BA, Lang PA, Kempe DS et al (2006) Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion. Am J Physiol Cell Physiol 290:C244-253 PubMed

Lang F, Lang E, Föller M (2012) Physiology and pathophysiology of eryptosis. Transfus Med Hemother 39:308–314 PubMed PMC

Fang M, Xia F, Chen Y et al (2022) Role of eryptosis in hemorrhagic stroke. Front Mol Neurosci 15:932931 PubMed PMC

Yue J, López JM (2020) Understanding MAPK signaling pathways in apoptosis. Int J Mol Sci 21(7):2346 PubMed PMC

Whitaker RH, Cook JG (2021) Stress relief techniques: p38 MAPK determines the balance of cell cycle and apoptosis pathways. Biomolecules 11:1444 PubMed PMC

Cai B, Chang SH, Becker EB, Bonni A, Xia Z (2006) p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem 281:25215–25222 PubMed

Shao Q, Han F, Peng S, He B (2016) Nur77 inhibits oxLDL induced apoptosis of macrophages via the p38 MAPK signaling pathway. Biochem Biophys Res Commun 471:633–638 PubMed

Hazegh K, Fang F, Kelly K et al (2022) Erythrocyte mitogen-activated protein kinases mediate hemolytic events under osmotic and oxidative stress and in hemolytic diseases. Cell Signal 99:110450 PubMed PMC

Wu W, Sun XH (2012) Janus kinase 3: the controller and the controlled. Acta Biochim Biophys Sin (Shanghai) 44:187–196 PubMed

Bhavsar SK, Gu S, Bobbala D, Lang F (2011) Janus kinase 3 is expressed in erythrocytes, phosphorylated upon energy depletion and involved in the regulation of suicidal erythrocyte death. Cell Physiol Biochem 27:547–556 PubMed

Katahira I, Neo S, Nagane M, Miyagi S, Hisasue M, Bhuyan AAM (2020) Characterization of suicidal erythrocyte death (Eryptosis) in dogs. Cell Physiol Biochem 54:605–614 PubMed

Nagy ZS, Ross JA, Rodriguez G, Bader J, Dimmock J, Kirken RA (2010) Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways. FEBS Lett 584:1515–1520 PubMed PMC

Bodaar K, Yamagata N, Barthe A et al (2022) JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia. Leukemia 36:1499–1507 PubMed PMC

Lang E, Zelenak C, Eberhard M et al (2015) Impact of cyclin-dependent kinase CDK4 inhibition on eryptosis. Cell Physiol Biochem 37:1178–1186 PubMed

Skowron MA, Vermeulen M, Winkelhausen A et al (2020) CDK4/6 inhibition presents as a therapeutic option for paediatric and adult germ cell tumours and induces cell cycle arrest and apoptosis via canonical and non-canonical mechanisms. Br J Cancer 123:378–391 PubMed PMC

Thoms HC, Dunlop MG, Stark LA (2007) CDK4 inhibitors and apoptosis: a novel mechanism requiring nucleolar targeting of RelA. Cell Cycle 6:1293–1297 PubMed

Guney Eskiler G, Deveci Ozkan A, Haciefendi A, Bilir C (2022) Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro. Transl Oncol 15:101243 PubMed

Retzer-Lidl M, Schmid RM, Schneider G (2007) Inhibition of CDK4 impairs proliferation of pancreatic cancer cells and sensitizes towards TRAIL-induced apoptosis via downregulation of survivin. Int J Cancer 121:66–75 PubMed

Föller M, Sopjani M, Koka S et al (2009) Regulation of erythrocyte survival by AMP-activated protein kinase. Faseb j 23:1072–1080 PubMed

Zelenak C, Föller M, Velic A et al (2011) Proteome analysis of erythrocytes lacking AMP-activated protein kinase reveals a role of PAK2 kinase in eryptosis. J Proteome Res 10:1690–1697 PubMed

Grenier A, Poulain L, Mondesir J et al (2022) AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia. Cell Rep 38:110197 PubMed

Villanueva-Paz M, Cotán D, Garrido-Maraver J et al (2016) AMPK regulation of cell growth, apoptosis, autophagy, and bioenergetics. Exp Suppl 107:45–71 PubMed

Repnik U, Turk B (2010) Lysosomal-mitochondrial cross-talk during cell death. Mitochondrion 10:662–669 PubMed

Bock FJ, Tait SWG (2020) Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol 21:85–100 PubMed

Wang F, Gómez-Sintes R, Boya P (2018) Lysosomal membrane permeabilization and cell death. Traffic 19:918–931 PubMed

Yamashita G, Takano N, Kazama H, Tsukahara K, Miyazawa K (2022) p53 regulates lysosomal membrane permeabilization as well as cytoprotective autophagy in response to DNA-damaging drugs. Cell Death Discovery 8:502 PubMed PMC

Eriksson I, Vainikka L, Persson HL, Öllinger K (2023) Real-time monitoring of lysosomal membrane permeabilization using acridine orange. Methods Protoc 6(4):72 PubMed PMC

Repnik U, Hafner Česen M, Turk B (2014) Lysosomal membrane permeabilization in cell death: concepts and challenges. Mitochondrion 19:49–57 PubMed

Zivot A, Lipton JM, Narla A, Blanc L (2018) Erythropoiesis: insights into pathophysiology and treatments in 2017. Mol Med 24:11 PubMed PMC

Chaichompoo P, Svasti S, Smith DR (2022) The roles of mitophagy and autophagy in ineffective erythropoiesis in β-thalassemia. Int J Mol Sci 23(18):10811 PubMed PMC

Toda S, Nishi C, Yanagihashi Y, Segawa K, Nagata S (2015) Clearance of apoptotic cells and pyrenocytes. Curr Top Dev Biol 114:267–295 PubMed

Diwan A, Koesters AG, Capella D, Geiger H, Kalfa TA, Dorn GW 2nd (2008) Targeting erythroblast-specific apoptosis in experimental anemia. Apoptosis 13:1022–1030 PubMed PMC

Pellegrin S, Heesom KJ, Satchwell TJ et al (2012) Differential proteomic analysis of human erythroblasts undergoing apoptosis induced by epo-withdrawal. PLoS ONE 7:e38356 PubMed PMC

Ma J, Ji L, Li Z et al (2019) Downregulation of intrinsic apoptosis pathway in erythroblasts contributes to excessive erythrocytosis of chronic mountain sickness. Blood Cells Mol Dis 76:25–31 PubMed

Gallivan A, Alejandro M, Kanu A et al (2023) Reticulocyte mitochondrial retention increases reactive oxygen species and oxygen consumption in mouse models of sickle cell disease and phlebotomy-induced anemia. Exp Hematol 122:55–62 PubMed

Stockwell BR (2022) Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications. Cell 185:2401–2421 PubMed PMC

Chen Z, Jiang J, Fu N, Chen L (2022) Targetting ferroptosis for blood cell-related diseases. J Drug Target 30:244–258 PubMed

Nishizawa H, Matsumoto M, Shindo T et al (2020) Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. J Biol Chem 295:69–82 PubMed

Nishizawa H, Yamanaka M, Igarashi K (2023) Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal. Febs j 290:1688–1704 PubMed

Zargarian S, Shlomovitz I, Erlich Z et al (2017) Phosphatidylserine externalization, “necroptotic bodies” release, and phagocytosis during necroptosis. PLoS Biol 15:e2002711 PubMed PMC

Bertheloot D, Latz E, Franklin BS (2021) Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18:1106–1121 PubMed PMC

Boulet C, Doerig CD, Carvalho TG (2018) Manipulating Eryptosis of Human Red Blood Cells: A Novel Antimalarial Strategy? Front Cell Infect Microbiol 8:419 PubMed PMC

Boulet C, Gaynor TL, Carvalho TG (2021) Eryptosis and malaria: new experimental guidelines and re-evaluation of the antimalarial potential of eryptosis inducers. Front Cell Infect Microbiol 11:630812 PubMed PMC

Lang PA, Huober J, Bachmann C et al (2006) Stimulation of erythrocyte phosphatidylserine exposure by paclitaxel. Cell Physiol Biochem 18:151–164 PubMed

Lui JC, Wong JW, Suen YK, Kwok TT, Fung KP, Kong SK (2007) Cordycepin induced eryptosis in mouse erythrocytes through a Ca2+-dependent pathway without caspase-3 activation. Arch Toxicol 81:859–865 PubMed

Niemoeller OM, Foller M, Lang C, Huber SM, Lang F (2008) Retinoic acid induced suicidal erythrocyte death. Cell Physiol Biochem 21:193–202 PubMed

Foller M, Mahmud H, Gu S et al (2009) Participation of leukotriene C(4) in the regulation of suicidal erythrocyte death. J Physiol Pharmacol 60:135–143 PubMed

Jilani K, Qadri SM, Lang E et al (2011) Stimulation of erythrocyte phospholipid scrambling by enniatin A. Mol Nutr Food Res 55(Suppl 2):S294-302 PubMed

Lang E, Jilani K, Zelenak C et al (2011) Stimulation of suicidal erythrocyte death by benzethonium. Cell Physiol Biochem 28:347–354 PubMed

Fırat U, Kaya S, Cim A et al (2012) Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats. Exp Diabetes Res 2012:316384 PubMed PMC

Gao M, Cheung KL, Lau IP et al (2012) Polyphyllin D induces apoptosis in human erythrocytes through Ca2 PubMed

Gao M, Wong SY, Lau PM, Kong SK (2013) Ferutinin induces in vitro eryptosis/erythroptosis in human erythrocytes through membrane permeabilization and calcium influx. Chem Res Toxicol 26:1218–1228 PubMed

Lang E, Modicano P, Arnold M et al (2013) Effect of thioridazine on erythrocytes. Toxins (Basel) 5:1918–1931 PubMed

Jacobi J, Lang E, Bissinger R et al (2014) Stimulation of erythrocyte cell membrane scrambling by mitotane. Cell Physiol Biochem 33:1516–1526 PubMed

Hoque M, Nanduri R, Gupta J, Mahajan S, Gupta P, Saleemuddin M (2015) Oleic acid complex of bovine α-lactalbumin induces eryptosis in human and other erythrocytes by a Ca(2+)-independent mechanism. Biochim Biophys Acta 1850:1729–1739 PubMed

Bissinger R, Al Mamun Bhuyan A, Signoretto E, Lang F (2016) Stimulating effect of elvitegravir on suicidal erythrocyte death. Cell Physiol Biochem 38:1111–1120 PubMed

Maćczak A, Cyrkler M, Bukowska B, Michałowicz J (2016) Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study). J Hazard Mater 307:328–335 PubMed

Shan F, Yang R, Ji T, Jiao F (2016) Vitamin C inhibits aggravated eryptosis by hydrogen peroxide in glucose-6-phosphated dehydrogenase deficiency. Cell Physiol Biochem 39:1453–1462 PubMed

Michałowicz J, Włuka A, Cyrkler M, Maćczak A, Sicińska P, Mokra K (2018) Phenol and chlorinated phenols exhibit different apoptotic potential in human red blood cells (in vitro study). Environ Toxicol Pharmacol 61:95–101 PubMed

Sicińska P (2018) Di-n-butyl phthalate, butylbenzyl phthalate and their metabolites induce haemolysis and eryptosis in human erythrocytes. Chemosphere 203:44–53 PubMed

Alfhili MA, Nkany MB, Weidner DA, Lee MH (2019) Stimulation of eryptosis by broad-spectrum insect repellent N, N-Diethyl-3-methylbenzamide (DEET). Toxicol Appl Pharmacol 370:36–43 PubMed

Alfhili MA, Weidner DA, Lee MH (2019) Disruption of erythrocyte membrane asymmetry by triclosan is preceded by calcium dysregulation and p38 MAPK and RIP1 stimulation. Chemosphere 229:103–111 PubMed

Alamri HS, Alsughayyir J, Akiel M et al (2021) Stimulation of calcium influx and CK1α by NF-κB antagonist [6]-Gingerol reprograms red blood cell longevity. J Food Biochem 45:e13545 PubMed

Alfhili MA, Alsughayyir J, Basudan AM (2021) Reprogramming of erythrocyte lifespan by NFκB-TNFα naphthoquinone antagonist β-lapachone is regulated by calcium overload and CK1α. J Food Biochem 45:e13710 PubMed

Alfhili MA, Alamri HS, Alsughayyir J, Basudan AM (2022) Induction of hemolysis and eryptosis by occupational pollutant nickel chloride is mediated through calcium influx and p38 MAP kinase signaling. Int J Occup Med Environ Health 35:1–11 PubMed PMC

Niemoeller OM, Akel A, Lang PA et al (2006) Induction of eryptosis by cyclosporine. Naunyn Schmiedebergs Arch Pharmacol 374:41–49 PubMed

Nicolay JP, Schneider J, Niemoeller OM et al (2006) Stimulation of suicidal erythrocyte death by methylglyoxal. Cell Physiol Biochem 18:223–232 PubMed

Nicolay JP, Gatz S, Liebig G, Gulbins E, Lang F (2007) Amyloid induced suicidal erythrocyte death. Cell Physiol Biochem 19:175–184 PubMed

Mahmud H, Föller M, Lang F (2008) Stimulation of erythrocyte cell membrane scrambling by methyldopa. Kidney Blood Press Res 31:299–306 PubMed

Qadri SM, Mahmud H, Föller M, Lang F (2009) Thymoquinone-induced suicidal erythrocyte death. Food Chem Toxicol 47:1545–1549 PubMed

Jilani K, Qadri SM, Lang F (2013) Geldanamycin-induced phosphatidylserine translocation in the erythrocyte membrane. Cell Physiol Biochem 32:1600–1609 PubMed

Voelkl J, Alzoubi K, Mamar AK, Ahmed MS, Abed M, Lang F (2013) Stimulation of suicidal erythrocyte death by increased extracellular phosphate concentrations. Kidney Blood Press Res 38:42–51 PubMed

Arnold M, Bissinger R, Lang F (2014) Mitoxantrone-induced suicidal erythrocyte death. Cell Physiol Biochem 34:1756–1767 PubMed

Bissinger R, Fischer S, Jilani K, Lang F (2014) Stimulation of erythrocyte death by phloretin. Cell Physiol Biochem 34:2256–2265 PubMed

Bissinger R, Malik A, Warsi J, Jilani K, Lang F (2014) Piperlongumine-induced phosphatidylserine translocation in the erythrocyte membrane. Toxins (Basel) 6:2975–2988 PubMed

Alzoubi K, Egler J, Abed M, Lang F (2015) Enhanced eryptosis following auranofin exposure. Cell Physiol Biochem 37:1018–1028 PubMed

Attanasio P, Bissinger R, Haverkamp W, Pieske B, Wutzler A, Lang F (2015) Enhanced suicidal erythrocyte death in acute cardiac failure. Eur J Clin Invest 45:1316–1324 PubMed

Bouguerra G, Aljanadi O, Bissinger R, Abbès S, Lang F (2015) Embelin-induced phosphatidylserine translocation in the erythrocyte cell membrane. Cell Physiol Biochem 37:1629–1640 PubMed

Calabrò S, Alzoubi K, Bissinger R, Faggio C, Lang F (2015) Stimulation of suicidal erythrocyte death by ellipticine. Basic Clin Pharmacol Toxicol 116:485–492 PubMed

Lupescu A, Bissinger R, Goebel T et al (2015) Enhanced suicidal erythrocyte death contributing to anemia in the elderly. Cell Physiol Biochem 36:773–783 PubMed

Bissinger R, Artunc F, Qadri SM, Lang F (2016) Reduced erythrocyte survival in uremic patients under hemodialysis or peritoneal dialysis. Kidney Blood Press Res 41:966–977 PubMed

Bissinger R, Schumacher C, Qadri SM et al (2016) Enhanced eryptosis contributes to anemia in lung cancer patients. Oncotarget 7:14002–14014 PubMed PMC

Signoretto E, Castagna M, Lang F (2016) Stimulation of eryptosis, the suicidal erythrocyte death by piceatannol. Cell Physiol Biochem 38:2300–2310 PubMed

Zierle J, Bissinger R, Bouguerra G, Abbès S, Lang F (2016) Triggering of suicidal erythrocyte death by regorafenib. Cell Physiol Biochem 38:160–172 PubMed

Alvarez-Sala A, López-García G, Attanzio A et al (2018) Effects of plant sterols or β-cryptoxanthin at physiological serum concentrations on suicidal erythrocyte death. J Agric Food Chem 66:1157–1166 PubMed

du Plooy JN, Bester J, Pretorius E (2018) Eryptosis in haemochromatosis: implications for rheology. Clin Hemorheol Microcirc 69:457–469 PubMed

Kempe-Teufel DS, Bissinger R, Qadri SM, Wagner R, Peter A, Lang F (2018) Cellular markers of eryptosis are altered in type 2 diabetes. Clin Chem Lab Med 56:e177–e180 PubMed

Bouguerra G, Talbi K, Trabelsi N et al (2021) Enhanced eryptosis in glucose-6-phosphate dehydrogenase deficiency. Cell Physiol Biochem 55:761–772 PubMed

Gok MG, Paydas S, Boral B, Onan E, Kaya B (2022) Evaluation of eryptosis in patients with chronic kidney disease. Int Urol Nephrol 54:2919–2928 PubMed

Song P, Cai YC, Chen MX, Chen SH, Chen JX (2022) Enhanced phosphatidylserine exposure and erythropoiesis in Babesia microti-infected mice. Front Microbiol 13:1083467 PubMed

Alfhili MA, Alsughayyir J (2023) Metabolic exhaustion and casein kinase 1α drive deguelin-induced premature red blood cell death. Xenobiotica 53:1–9

Cell death signaling in human erythron: erythrocytes lose the complexity of cell death machinery upon maturation

Erythronecroptosis: an overview of necroptosis or programmed necrosis in red blood cells

GdVO4:Eu3+ and LaVO4:Eu3+ Nanoparticles Exacerbate Oxidative Stress in L929 Cells: Potential Implications for Cancer Therapy