Skip to main content
SpringerLink
Log in

Cell Death in Ischemia-Reperfusion-Induced Liver Injury

  • Chapter
  • First Online:
Cellular Injury in Liver Diseases

Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

  • 857 Accesses

Abstract

Hepatic ischemia-reperfusion injury (IRI) is incurred in a variety of disease processes and leads to profound local and systemic effects through hepatic cell death and the associated inflammatory response. Understanding mechanisms of cell death after hepatic IRI is essential for developing strategies to ameliorate its widespread effects. Classically, cell death has been attributed to apoptotic and necrotic pathways, both of which remain important in IRI. However, as we describe, numerous other pathways, including necroptosis, ferroptosis, pyroptosis, autophagy, and NETosis, may also play a role in this disease process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ASC:

Apoptosis-associated speck-like protein-containing CARD

Atg:

Autophagy

ATP:

Adenosine triphosphate

Bax:

Bcl-2-associated X

Bcl-2:

B-cell lymphoma 2

BECN1:

Beclin-1

Bid:

BH3-interacting domain

CARS:

Cysteinyl-tRNA-synthetase

c-FLIP:

Cellular FLICE-like inhibitory protein

DAMP:

Damage-associated molecular pattern

DC:

Dendritic cell

FADD:

Fas-associated death domain

GPX4:

Glutathione peroxidase 4

GSH:

Glutathione

GSSG:

Oxidized glutathione

HMGB1:

High-mobility group box protein 1

HSPB1:

Heat shock protein beta 1

IRI:

Ischemia-reperfusion injury

LSEC:

Liver sinusoidal endothelial cell

MLKL:

Mixed linkage kinase domain-like

MPT:

Mitochondrial permeability transition

NASH:

Non-alcoholic steatohepatitis

NET:

Neutrophil extracellular trap

NLRP3:

Nucleotide-binding domain, leucine-rich repeat containing protein 3

NOX:

Nitrogen oxide

NRF2:

Nuclear respiratory factor 2

PAD4:

Peptidyl-arginine-deaminase-4

PI3K:

Phosphatidylinositol-3-kinase

PKB:

Protein kinase B

PTEN:

Phosphate and tensin homologue

RIPK:

Receptor-interacting protein kinase

ROS:

Reactive oxidant species

RSL:

RAS-selective lethal

TFR1:

Transferrin receptor 1

TLR:

Toll-like receptor

TRADD:

TNF-receptor-associated death domain

TRAIL:

TNF-related apoptosis-inducing ligand

TUNEL:

Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling

VDAC:

Voltage-dependent anion channel

References

  • Baehrecke EH (2005) Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 6(6):505–510

    Article  CAS  PubMed  Google Scholar 

  • Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79(4):1127–1155

    CAS  PubMed  Google Scholar 

  • Brenner C, Galluzzi L, Kepp O, Kroemer G (2013) Decoding cell death signals in liver inflammation. J Hepatol 59(3):583–594

    Article  CAS  PubMed  Google Scholar 

  • Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535

    Article  CAS  PubMed  Google Scholar 

  • Broz P, von Moltke J, Jones JW, Vance RE, Monack DM (2010) Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe 8(6):471–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ (1989) Reperfusion injury to endothelial cells following cold ischemic storage of rat livers. Hepatology 10(3):292–299

    Article  CAS  PubMed  Google Scholar 

  • Camilleri-Broet S, Vanderwerff H, Caldwell E, Hockenbery D (1998) Distinct alterations in mitochondrial mass and function characterize different models of apoptosis. Exp Cell Res 239(2):277–292

    Article  CAS  PubMed  Google Scholar 

  • Cao JY, Dixon SJ (2016) Mechanisms of ferroptosis. Cell Mol Life Sci 73(11–12):2195–2209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cookson BT, Brennan MA (2001) Pro-inflammatory programmed cell death. Trends Microbiol 9(3):113–114

    Article  CAS  PubMed  Google Scholar 

  • Cursio R, Colosetti P, Gugenheim J (2015) Autophagy and liver ischemia-reperfusion injury. Biomed Res Int 2015:417590

    PubMed  PubMed Central  Google Scholar 

  • Cursio R, Gugenheim J, Ricci JE, Crenesse D, Rostagno P, Maulon L, Saint-Paul MC, Ferrua B, Auberger AP (1999) A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis. FASEB J 13(2):253–261

    CAS  PubMed  Google Scholar 

  • Czaja MJ, Ding WX, Donohue TM Jr, Friedman SL, Kim JS, Komatsu M, Lemasters JJ, Lemoine A, Lin JD, Ou JH, Perlmutter DH, Randall G, Ray RB, Tsung A, Yin XM (2013) Functions of autophagy in normal and diseased liver. Autophagy 9(8):1131–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dickson RC, Bronk SF, Gores GJ (1992) Glycine cytoprotection during lethal hepatocellular injury from adenosine triphosphate depletion. Gastroenterology 102(6):2098–2107

    Article  CAS  PubMed  Google Scholar 

  • Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3):285–296

    Article  CAS  PubMed  Google Scholar 

  • Edgeworth JD, Spencer J, Phalipon A, Griffin GE, Sansonetti PJ (2002) Cytotoxicity and interleukin-1beta processing following Shigella flexneri infection of human monocyte-derived dendritic cells. Eur J Immunol 32(5):1464–1471

    Article  CAS  PubMed  Google Scholar 

  • Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, Rosenberg S, Zhang J, Alnemri ES (2007) The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ 14(9):1590–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fink SL, Bergsbaken T, Cookson BT (2008) Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci U S A 105(11):4312–4317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fink SL, Cookson BT (2006) Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8(11):1812–1825

    Article  CAS  PubMed  Google Scholar 

  • Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E, Basavarajappa D, Radmark O, Kobayashi S, Seibt T, Beck H, Neff F, Esposito I, Wanke R, Forster H, Yefremova O, Heinrichmeyer M, Bornkamm GW, Geissler EK, Thomas SB, Stockwell BR, O’Donnell VB, Kagan VE, Schick JA, Conrad M (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16(12):1180–1191

    Article  CAS  PubMed  Google Scholar 

  • Go KL, Lee S, Zendejas I, Behrns KE, Kim JS (2015) Mitochondrial dysfunction and autophagy in hepatic ischemia/reperfusion injury. Biomed Res Int 2015:183469

    Article  PubMed  PubMed Central  Google Scholar 

  • Gujral JS, Bucci TJ, Farhood A, Jaeschke H (2001) Mechanism of cell death during warm hepatic ischemia-reperfusion in rats: apoptosis or necrosis? Hepatology 33(2):397–405

    Article  CAS  PubMed  Google Scholar 

  • Hatano E, Bradham CA, Stark A, Iimuro Y, Lemasters JJ, Brenner DA (2000) The mitochondrial permeability transition augments Fas-induced apoptosis in mouse hepatocytes. J Biol Chem 275(16):11814–11823

    Article  CAS  PubMed  Google Scholar 

  • Hayano M, Yang WS, Corn CK, Pagano NC, Stockwell BR (2016) Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ 23(2):270–278

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Chen HW, Evankovich J, Yan W, Rosborough BR, Nace GW, Ding Q, Loughran P, Beer-Stolz D, Billiar TR, Esmon CT, Tsung A (2013) Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury. J Immunol 191(5):2665–2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang H, Tohme S, Al-Khafaji AB, Tai S, Loughran P, Chen L, Wang S, Kim J, Billiar T, Wang Y, Tsung A (2015) Damage-associated molecular pattern-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury. Hepatology 62(2):600–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaeschke H (2006) Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am J Physiol Gastrointest Liver Physiol 290(6):G1083–G1088

    Article  CAS  PubMed  Google Scholar 

  • Jaeschke H, Lemasters JJ (2003) Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury. Gastroenterology 125(4):1246–1257

    Article  CAS  PubMed  Google Scholar 

  • Jaeschke H, Woolbright BL (2012) Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplant Rev (Orlando) 26(2):103–114

    Article  Google Scholar 

  • Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R, Gu W (2015) Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520(7545):57–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaczmarek A, Vandenabeele P, Krysko DV (2013) Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38(2):209–223

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JS, Nitta T, Mohuczy D, O’Malley KA, Moldawer LL, Dunn WA Jr, Behrns KE (2008) Impaired autophagy: a mechanism of mitochondrial dysfunction in anoxic rat hepatocytes. Hepatology 47(5):1725–1736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim KH, Lee MS (2014) Autophagy—a key player in cellular and body metabolism. Nat Rev Endocrinol 10(6):322–337

    Article  CAS  PubMed  Google Scholar 

  • Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290(5497):1717–1721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohli V, Selzner M, Madden JF, Bentley RC, Clavien PA (1999) Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation 67(8):1099–1105

    Article  CAS  PubMed  Google Scholar 

  • Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH (2000) Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 7(12):1166–1173

    Article  CAS  PubMed  Google Scholar 

  • Ladoire S, Hannani D, Vetizou M, Locher C, Aymeric L, Apetoh L, Kepp O, Kroemer G, Ghiringhelli F, Zitvogel L (2014) Cell-death-associated molecular patterns as determinants of cancer immunogenicity. Antioxid Redox Signal 20(7):1098–1116

    Article  CAS  PubMed  Google Scholar 

  • Lau A, Wang S, Jiang J, Haig A, Pavlosky A, Linkermann A, Zhang ZX, Jevnikar AM (2013) RIPK3-mediated necroptosis promotes donor kidney inflammatory injury and reduces allograft survival. Am J Transplant 13(11):2805–2818

    Article  CAS  PubMed  Google Scholar 

  • Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185(8):1481–1486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemasters JJ (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 8(1):3–5

    Article  CAS  PubMed  Google Scholar 

  • Lemasters JJ, DiGuiseppi J, Nieminen AL, Herman B (1987) Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes. Nature 325(6099):78–81

    Article  CAS  PubMed  Google Scholar 

  • Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, Chan FK, Wu H (2012) The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150(2):339–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linkermann A, Brasen JH, Himmerkus N, Liu S, Huber TB, Kunzendorf U, Krautwald S (2012) Rip1 (receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury. Kidney Int 81(8):751–761

    Article  CAS  PubMed  Google Scholar 

  • Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370(5):455–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Louandre C, Ezzoukhry Z, Godin C, Barbare JC, Maziere JC, Chauffert B, Galmiche A (2013) Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer 133(7):1732–1742

    Article  CAS  PubMed  Google Scholar 

  • Magna M, Pisetsky DS (2016) The Alarmin Properties of DNA and DNA-associated Nuclear Proteins. Clin Ther 38(5):1029–1041

    Article  CAS  PubMed  Google Scholar 

  • Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146(1):3–15

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malhi H, Gores GJ, Lemasters JJ (2006) Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology 43(2 Suppl 1):S31–S44

    Article  CAS  PubMed  Google Scholar 

  • Marsh DC, Vreugdenhil PK, Mack VE, Belzer FO, Southard JH (1993) Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress. Hepatology 17(1):91–98

    Article  CAS  PubMed  Google Scholar 

  • Mathew R, Karantza-Wadsworth V, White E (2007) Role of autophagy in cancer. Nat Rev Cancer 7(12):961–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miao EA, Rajan JV, Aderem A (2011) Caspase-1-induced pyroptotic cell death. Immunol Rev 243(1):206–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nastos C, Kalimeris K, Papoutsidakis N, Tasoulis MK, Lykoudis PM, Theodoraki K, Nastou D, Smyrniotis V, Arkadopoulos N (2014) Global consequences of liver ischemia/reperfusion injury. Oxidative Med Cell Longev 2014:906965

    Article  Google Scholar 

  • Natori S, Selzner M, Valentino KL, Fritz LC, Srinivasan A, Clavien PA, Gores GJ (1999) Apoptosis of sinusoidal endothelial cells occurs during liver preservation injury by a caspase-dependent mechanism. Transplantation 68(1):89–96

    Article  CAS  PubMed  Google Scholar 

  • Nieminen AL, Gores GJ, Wray BE, Tanaka Y, Herman B, Lemasters JJ (1988) Calcium dependence of bleb formation and cell death in hepatocytes. Cell Calcium 9(5–6):237–246

    Article  CAS  PubMed  Google Scholar 

  • Nishimura Y, Lemasters JJ (2001) Glycine blocks opening of a death channel in cultured hepatic sinusoidal endothelial cells during chemical hypoxia. Cell Death Differ 8(8):850–858

    Article  CAS  PubMed  Google Scholar 

  • Nystrom S, Antoine DJ, Lundback P, Lock JG, Nita AF, Hogstrand K, Grandien A, Erlandsson-Harris H, Andersson U, Applequist SE (2013) TLR activation regulates damage-associated molecular pattern isoforms released during pyroptosis. EMBO J 32(1):86–99

    Article  PubMed  Google Scholar 

  • Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y, Itoh N, Suda T, Nagata S (1993) Lethal effect of the anti-Fas antibody in mice. Nature 364(6440):806–809

    Article  CAS  PubMed  Google Scholar 

  • Paxian M, Bauer I, Rensing H, Jaeschke H, Mautes AE, Kolb SA, Wolf B, Stockhausen A, Jeblick S, Bauer M (2003) Recovery of hepatocellular ATP and “pericentral apoptosis” after hemorrhage and resuscitation. FASEB J 17(9):993–1002

    Article  CAS  PubMed  Google Scholar 

  • Peralta C, Jimenez-Castro MB, Gracia-Sancho J (2013) Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu. J Hepatol 59(5):1094–1106

    Article  PubMed  Google Scholar 

  • Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P (2000) Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 275(2):992–998

    Google Scholar 

  • Quesnelle KM, Bystrom PV, Toledo-Pereyra LH (2015) Molecular responses to ischemia and reperfusion in the liver. Arch Toxicol 89(5):651–657

    Article  CAS  PubMed  Google Scholar 

  • Ratziu V, Goodman Z, Sanyal A (2015) Current efforts and trends in the treatment of NASH. J Hepatol 62(1 Suppl):S65–S75

    Article  CAS  PubMed  Google Scholar 

  • Richter C, Schweizer M, Cossarizza A, Franceschi C (1996) Control of apoptosis by the cellular ATP level. FEBS Lett 378(2):107–110

    Article  CAS  PubMed  Google Scholar 

  • Sasaki H, Matsuno T, Tanaka N, Orita K (1996) Activation of apoptosis during the reperfusion phase after rat liver ischemia. Transplant Proc 28(3):1908–1909

    CAS  PubMed  Google Scholar 

  • Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17(6):1675–1687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sindram D, Porte RJ, Hoffman MR, Bentley RC, Clavien PA (2000) Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver. Gastroenterology 118(1):183–191

    Article  CAS  PubMed  Google Scholar 

  • Sindram D, Porte RJ, Hoffman MR, Bentley RC, Clavien PA (2001) Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury. FASEB J 15(7):1230–1232

    CAS  PubMed  Google Scholar 

  • Smith CC, Davidson SM, Lim SY, Simpkin JC, Hothersall JS, Yellon DM (2007) Necrostatin: a potentially novel cardioprotective agent? Cardiovasc Drugs Ther 21(4):227–233

    Article  CAS  PubMed  Google Scholar 

  • Stehlik C, Lee SH, Dorfleutner A, Stassinopoulos A, Sagara J, Reed JC (2003) Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation. J Immunol 171(11):6154–6163

    Article  CAS  PubMed  Google Scholar 

  • Sun X, Ou Z, Xie M, Kang R, Fan Y, Niu X, Wang H, Cao L, Tang D (2015) HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34(45):5617–5625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tait SW, Ichim G, Green DR (2014) Die another way—non-apoptotic mechanisms of cell death. J Cell Sci 127(Pt 10):2135–2144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng X, Degterev A, Jagtap P, Xing X, Choi S, Denu R, Yuan J, Cuny GD (2005) Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett 15(22):5039–5044

    Article  CAS  PubMed  Google Scholar 

  • Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze MT, Yang H, Li J, Tracey KJ, Geller DA, Billiar TR (2005) The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med 201(7):1135–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11(10):700–714

    Article  CAS  PubMed  Google Scholar 

  • Vanlangenakker N, Bertrand MJ, Bogaert P, Vandenabeele P, Vanden Berghe T (2011) TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis 2:e230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vigil D, Cherfils J, Rossman KL, Der CJ (2010) Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer 10(12):842–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallach D, Kang TB, Dillon CP, Green DR (2016) Programmed necrosis in inflammation: toward identification of the effector molecules. Science 352(6281):aaf2154

    Article  PubMed  Google Scholar 

  • Wang JH, Ahn IS, Fischer TD, Byeon JI, Dunn WA Jr, Behrns KE, Leeuwenburgh C, Kim JS (2011) Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of mice. Gastroenterology 141(6):2188–2199. e2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X (2001) The expanding role of mitochondria in apoptosis. Genes Dev 15(22):2922–2933

    CAS  PubMed  Google Scholar 

  • Watson PR, Gautier AV, Paulin SM, Bland AP, Jones PW, Wallis TS (2000) Salmonella enterica serovars Typhimurium and Dublin can lyse macrophages by a mechanism distinct from apoptosis. Infect Immun 68(6):3744–3747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinberg JM, Davis JA, Abarzua M, Rajan T (1987) Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules. J Clin Invest 80(5):1446–1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE (2014) NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 59(3):898–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, Kang R, Tang D (2016) Ferroptosis: process and function. Cell Death Differ 23(3):369–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447(7146):864–868

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156(1–2):317–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang WS, Stockwell BR (2008) Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 15(3):234–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin XM (2000) Bid, a critical mediator for apoptosis induced by the activation of Fas/TNF-R1 death receptors in hepatocytes. J Mol Med (Berl) 78(4):203–211

    Article  CAS  Google Scholar 

  • Yipp BG, Kubes P (2013) NETosis: how vital is it? Blood 122(16):2784–2794

    Article  CAS  PubMed  Google Scholar 

  • Zahrebelski G, Nieminen AL, al-Ghoul K, Qian T, Herman B, Lemasters JJ (1995) Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study. Hepatology 21(5):1361–1372

    CAS  PubMed  Google Scholar 

  • Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW (2013) Ischaemia-reperfusion injury in liver transplantation—from bench to bedside. Nat Rev Gastroenterol Hepatol 10(2):79–89

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Ueki S, Kimura S, Yoshida O, Castellaneta A, Ozaki KS, Demetris AJ, Ross M, Vodovotz Y, Thomson AW, Stolz D B, Geller DA, Murase N (2013) Roles of dendritic cells in murine hepatic warm and liver transplantation-induced cold ischemia/reperfusion injury. Hepatology 57(4):1585–1596

    Article  CAS  PubMed  Google Scholar 

  • Zhao H, Jaffer T, Eguchi S, Wang Z, Linkermann A, Ma D (2015) Role of necroptosis in the pathogenesis of solid organ injury. Cell Death Dis 6:e1975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zychlinsky A, Prevost MC, Sansonetti PJ (1992) Shigella flexneri induces apoptosis in infected macrophages. Nature 358(6382):167–169

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Julie Goswami, Heather Waring, Allan Tsung M.D. & Hai Huang

  2. Division of Hepatobiliary and Pancreatic Surgery, University of Pittsburgh, 3471 Fifth Avenue, Suite 300, Pittsburgh, PA, 15213, USA

    Allan Tsung M.D.

Authors
  1. Julie Goswami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather Waring
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Allan Tsung M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allan Tsung M.D. .

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas, USA

    Wen-Xing Ding

  2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Xiao-Ming Yin

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Goswami, J., Waring, H., Tsung, A., Huang, H. (2017). Cell Death in Ischemia-Reperfusion-Induced Liver Injury. In: Ding, WX., Yin, XM. (eds) Cellular Injury in Liver Diseases. Cell Death in Biology and Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-53774-0_8

Download citation

Publish with us

Policies and ethics

Search

Navigation