Abstract
Cells employs many different mechanisms for their expiration. The best known and studied regulated cell death mechanism is apoptosis. Cell death subtypes, including regulated cell death (RCD), programmed cell death (PCD), and accidental cell death, are discussed. A discussion on and caution for the use of the term “necrosis” is included. Apoptosis was the earliest RCD mechanism shown in Jurkat cell responses to usEPs as determined by cytochrome c release and caspase activation. This apoptotic cell death was enhanced by usEP-induced supraelectroporation, as electric fields with nanosecond durations and short(fast) rise-fall times passed through the cell, while pulses with microsecond duration go around cells. However, using Jurkat clones that did and did not express APAF-1, which is an essential protein for apoptosome formation as a platform for caspase-9 and caspase-3 activation, it was also shown that usEPs induced caspase-dependent and caspase-independent cell death. A role for caspases depended on the usEP charging intensity with lower usEP impact causing caspase-dependent cell death while higher charging caused caspase-independent cell death. Although a full discussion of all RCD mechanisms is not included, evidence is presented that not all cell types responded to usEP by apoptotic cell death. The presence or absence of Ca2+ has an impact on the RCD mechanisms. Human triple-negative breast cancer cells expressed either or both necroptosis and parthanatos. Necroptosis is sometimes considered regulated necrosis because plasma membrane pores form from intracellular proteins. Finally, usEPs are also shown to induce cell responses downstream of toll-like receptors (TLRs). Considerations for immunogenic cell death (ICD) are also considered.
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References
Alemasova EE, Lavrik OI (2008) Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins. Nucleic Acids Res 47(8):3811–3827
Andrabi SA, Dawson TM, Dawson VL (2008) Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann NY Acad Sci 1147:233–241
Batista Napotnik T, Wu YH, Gundersen MA, Miklavčič D, Vernier PT (2012) Nanosecond electric pulses cause mitochondrial membrane permeabilization in Jurkat cells. Bioelectromagnetics 33(3):257–264
Beebe SJ, Fox PM, Rec LH, Buescher ES, Somers K, Schoenbach KH (2002) Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. IEEE Trans Plasma Sci 30:286–292
Beebe SJ, Fox PM, Rec LJ, Willis EL, Schoenbach KH (2003) Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J 17:1493–2145
Beebe SJ, Chen YJ, Sain NM, Schoenbach KH, Xiao S (2012) Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability.PLoS One 7(12):e51349
Beebe SJ, Sain NM, Ren W (2013) Induction of cell death mechanisms and apoptosis by nanosecond pulsed electric fields (nsPEFs). Cells 2:136–162
Broz P, Dixit VM (2005) Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 2016; 16, 407–420
Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15:269–290
Burdette DL, Vance RE (2013) STING and the innate immune response to nucleic acids in the cytosol. Nat Immunol 14:19–26
Chen X et al (2016) Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res 26:1007–1020
Cho YS et al (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123
Conradt B, Wu YC, Xue D (2016) Programmed cell death during caenorhabditis elegans development. Genetics 203(4):1533–1562
D’Arcy MS (2019) Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Review Cell Biol Int 43(6):582–592. https://doi.org/10.1002/cbin.11137
David KK, Andrabi SA, Dawson TM, Dawson VL (2009) Parthanatos, a messenger of death. Front Biosci (landmark Ed) 14:1116–1128
He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res 25(12):1285–1298
Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC, Shao F (2016) Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535(7610):111–116
Dondelinger Y, Declercq W, Montessuit S et al (2014) MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep 7(4):971–981
Estlack LE, Roth CC, Thompson GL 3rd, Lambert WA 3rd, Ibey BL (2014) Nanosecond pulsed electric fields modulate the expression of Fas/CD95 death receptor pathway regulators in U937 and Jurkat Cells. Apoptosis 19:1755–1768
Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074
Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M, Baehrecke EH, Bazan NG, Bertrand MJ, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Campanella M, Candi E, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, Di Daniele N, Dixit VM, Dynlacht BD, El-Deiry WS, Fimia GM, Flavell RA, Fulda S, Garrido C, Gougeon ML, Green DR, Gronemeyer H, Hajnoczky G, Hardwick JM, Hengartner MO, Ichijo H, Joseph B, Jost PJ, Kaufmann T, Kepp O, Klionsky DJ, Knight RA, Kumar S, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Lugli E, Madeo F, Malorni W, Marine JC, Martin SJ, Martinou JC, Medema JP, Meier P, Melino S, Mizushima N, Moll U, Muñoz-Pinedo C, Nuñez G, Oberst A, Panaretakis T, Penninger JM, Peter ME, Piacentini M, Pinton P, Prehn JH, Puthalakath H, Rabinovich GA, Ravichandran KS, Rizzuto R, Rodrigues CM, Rubinsztein DC, Rudel T, Shi Y, Simon HU, Stockwell BR, Szabadkai G, Tait SW, Tang HL, Tavernarakis N, Tsujimoto Y, Vanden Berghe T, Vandenabeele P, Villunger A, Wagner EF, Walczak H, White E, Wood WG, Yuan J, Zakeri Z, Zhivotovsky B, Melino G, Kroemer G (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22(1):58–73
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death
Gowrishankar TR, Esser AT, Vasilkoski Z, Smith KC, Weaver JC (2006) Microdosimetry for conventional and supra-electroporation in cells with organelles. Biochem Biophys Res Commun 341(4):1266–1276
Green DR (2005) Apoptotic pathways: ten minutes to dead. Cell 121(5):671–674
Hall EH, Schoenbach KH, Beebe SJ (2007) Nanosecond pulsed electric fields have differential effects on cells in the S-phase. DNA Cell Biol 26(3):160–171
He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137(6):1100–1111
He S, Liang Y, Shao F, Wang X (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci USA 108:20054–20059
Helgason E, Phung QT, Dueber EC (2013) Recent insights into the complexity of Tank-binding kinase 1 signaling networks: the emerging role of cellular localization in the activation and substrate specificity of TBK1. FEBS Lett 587(8):1230–1237
Hildebrand JM, Tanzer MC, Lucet IS et al (2014) Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci USA 111(42):15072–15077. https://doi.org/10.1073/pnas.1408987111
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1(6):489–495
Iwasaki A, Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nat Immunol 16(4):343–353
Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461
Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526(7575):666–671
Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N et al (2014) Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 3:e955691
Kerr JF (1971) Shrinkage necrosis: a distinct mode of cellular death. J Pathol. 105(1):13–20
Kerr JFR (2002) History of the events leading to the formulation of the apoptosis concept. Toxicology
Kerr JF, Searle J (1972) The digestion of cellular fragments within phagolysosomes in carcinoma cells. J Pathol 108(1):55–58
Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257
Kantari and Walczak (2011) Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 1813(4):558–563
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G (2009) Nomenclature Committee on Cell Death 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16(1):3–11
Kumar V, Abbas AK, Aster JC, Fausto N (2010) Robbins and Cotran pathologic basis of disease, 8th ed. Saunders/Elsevier, Philadelphia, PA, pp. 12–41. ISBN 978-1416031215
Li T, Chen LJ (2018) The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med 215(5):1287–1299
Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F, Prokai A, Zuchtriegel G, Krombach F, Welz PS, Weinlich R, Vanden Berghe T, Vandenabeele P, Pasparakis M, Bleich M, Weinberg JM, Reichel CA, Bräsen JH, Kunzendorf U, Anders HJ, Stockwell BR, Green DR, Krautwald S (2014) Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 111(47):16836–16841
Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J (2016) inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535(7610):153–158
Maier P, Hartmann L, Wenz F, Herskind C (2016) Cellular pathways in response to ionizing radiation and their targetability for tumor radiosensitization. Int J Mol Sci 17(1):102
Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146(1):3–15
Meissner F, Molawi K, Zychlinsky A (2008) Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9(8):866–872
Morotomi-Yano K, Oyadomari S, Akiyama H, Yano K (2012) Nanosecond pulsed electric fields act as a novel cellular stress that induces translational suppression accompanied by eIF2α phosphorylation and 4E-BP1 dephosphorylation. Exp Cell Res 318(14):1733–1744
Morotomi-Yano K, Akiyama H, Yano K (2013) Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells.Biochem Biophys Res Commun 438(3):557–562
Morotomi-Yano K, Akiyama H, Yano K (2014) Different involvement of extracellular calcium in two modes of cell death induced by nanosecond pulsed electric fields. Arch Biochem Biophys 555–556:47–54
Murphy JM, Czabotar PE, Hildebrand JM et al (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39(3):443–453. https://doi.org/10.1016/j.immuni.2013.06.018
Napoletano F, Baron O, Vandenabeele P, Mollereau B, Fanto M (2019) Intersections between Regulated Cell Death and Autophagy. Trends Cell Biol 29(4):323–338
Neutelings T, Lambert CA, Nusgens BV, Colige AC (2013) Effects of mild cold shock (25 °C) followed by warming up at 37 °C on the cellular stress response. PLoS ONE 8(7):e69687
O’Neill LA, Bryant CE, Doyle SL (2009) Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61(2):177–197
Pakhomov AG, Bowman AM, Ibey BL, Andre FM, Pakhomova ON, Schoenbach KH (2009) Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. Biochem Biophys Res Commun 385:181–186
Pakhomova ON, Gregory BW, Semenov I, Pakhomov AG (2013) Two modes of cell death caused by exposure to nanosecond pulsed electric field. PLoS One 8(7):e70278
Pakhomova ON, Gregory B, Semenov I, Pakhomov AG (2014) Calcium-mediated pore expansion and cell death following nanoelectroporation. Biochim Biophys Acta 1838(10):2547–2554
Parvathenani LK, Buescher ES, Chacon-Cruz E, Beebe SJ (1998) Type I cAMP-dependent protein kinase delays apoptosis in human neutrophils at a site upstream of caspase-3.J Biol Chem 273(12):6736–6743
Pascal JM (2018) The comings and goings of PARP-1 in response to DNA Damage—review. DNA Repair (amst) 71:177–182
Pasparakis M, Vandenabeele P (2015) Necroptosis and its role in inflammation. Nature 517:311–320
Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104
Platnich JM, Chung H, Lau A, Sandall CF, Bondzi-Simpson A, Chen HM, Komada T, Trotman-Grant AC, Brandelli JR, Chun J, Beck PL, Philpott DJ, Girardin SE, Ho M, Johnson RP, MacDonald JA, Armstrong GD, Muruve DA (2018) Shiga Toxin/lipopolysaccharide activates caspase-4 and gasdermin D to trigger mitochondrial reactive oxygen species upstream of the NLRP3 inflammasome. Cell Rep 25(6):1525-1536.e7
Rathkey JK, Zhao J, Liu Z, Chen Y, Yang J, Kondolf HC, Benson BL, Chirieleison SM, Huang AY, Dubyak GR, Xiao TS, Li X, Abbott DW (2018) Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol 3(26):eaat2738
Ren W, Beebe SJ (2011) An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma. Apoptosis 16(4):382–393
Ren W, Sain NM, Beebe SJ (2012) Nanosecond pulsed electric fields (nsPEFs) activate intrinsic caspase-dependent and caspase-independent cell death in Jurkat cells. Biochem Biophys Res Commun 421:808–812
Robinson N, Ganesan R, Hegedűs C, Kovács K, Kufer TA, Virág L (2019) Programmed necrotic cell death of macrophages: focus on pyroptosis, necroptosis, and parthanatos. Redox Biol. 26:101239
Ron D (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110(10):1383–1388
Schleich K, Warnken U, Fricker N, Oztürk S, Richter P, Kammerer K, Schnölzer M, Krammer PH, Lavrik IN (2012) Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol Cell 47(2):306–319
Schoenbach KH, Beebe SJ, Buescher ES (2001) Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 22:440–448
Schoenbach KH, Joshi RP, Kolb JF, Chen N, Stacey M, Blackmore PF, Buescher ES, Beebe SJ (2004) Ultrashort electrical pulses open a new gateway into biological cells. Proc of the IEEE 92:1122–1137
Schoenbach KH, Joshi RP, Beebe SJ, Baum CE (2009) A scaling law for membrane permeabilization with nanopulses. IEEE Trans Dielectrics Electrical Insul 16:1224–1235
Semenov I, Xiao S, Pakhomova ON, Pakhomov AG (2013) Recruitment of the intracellular Ca2+ by ultrashort electric stimuli: the impact of pulse duration. Cell Calcium 54(3):145–150
Shi J, Gao W, Shao F (2017) Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 42(4):245–254
Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171(2):273–285
Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G (2019) The molecular machinery of regulated cell death. Cell Res. 29(5):347–364
Vanden Berghe T, Vanlangenakker N, Parthoens E, Deckers W, Devos M, Festjens N, Guerin CJ, Brunk UT, Declercq W, Vandenabeele P (2010) Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ 17(6):922–930
Vernier PT, Sun Y, Gundersen MA (2006a) Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell Biol 7:37
Vernier PT, Ziegler MJ, Sun Y, Gundersen MA, Tieleman DP (2006b) Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid bilayers–in cells and in silico. Phys Biol. 3:233–247
Wang Y, Kim NS, Haince JS, Kang HC, David KK, Andrabi SA, Poirier GG, Dawson VL, Dawson TM (2011) Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1–dependent cell death (parthanatos). Sci Signal 4(167):ra20
Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54(1):133–146
Wang Z, Jiang H, Chen S, Du F, Wang X (2012) The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148(1–2):228–243
Wei H, Yu X (2016) Functions of PARylation in DNA damage repair pathways. Genomics Proteomics Bioinform 14(3):131–139
Wyllie AH, Kerr JF, Currie AR (1972) Cellular events in the adrenal cortex following ACTH deprivation. J Pathol 106(1):Pix
Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306
Wu J, Chen ZJ (2014) Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol 32:461–488
Zhang DW et al (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336
Zhang J, Yang Y, He W, Sun L (2016) Necrosome core machinery: MLKL. Cell Mol Life Sci 73(11–12):2153–2163
Zhang Y, Su SS, Zhao S, et al (2017) RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun 8:14329. https://doi.org/10.1038/ncomms14329
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Beebe, S.J. (2021). usEP Induce Regulated Cell Death Mechanisms. In: Ultrashort Electric Pulse Effects in Biology and Medicine. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-5113-5_9
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