Abstract
Reactive oxygen species (ROS) are chemically reactive by-products of normal aerobic metabolism and xenobiotic exposure. ROS produced during different cellular reactions can be either beneficial or harmful to the cells. At physiological concentrations, ROS function as second messengers in intracellular signaling. On the other hand, aberrance in redox balance leading to excessive ROS production may cause biochemical alterations and induce oxidative modification of cellular macromolecules leading to cell death. Apoptosis or programmed cell death is a well-regulated physiological process involved in the regulation of tissue homeostasis. Induction of apoptosis by extracellular and intracellular signals triggers apoptotic-signaling pathways. The two main apoptotic pathways recognized in general are the death receptor or extrinsic pathway and the mitochondrial or intrinsic pathway. The redox state of a cell plays a major role in the regulation of apoptosis in response to any external or internal stimuli. ROS can mediate apoptosis by regulating the expression of various pro-apoptotic proteins such as caspases or anti-apoptotic proteins such as B cell lymphoma-2 (Bcl-2) and cellular FLICE-inhibitory protein (c-FLIP). Overexpression of anti-apoptotic proteins and dysregulated apoptosis is associated with various pathologies including cancer. In this chapter, we focus on the key apoptotic mechanisms and proteins that are regulated by the cellular redox state.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abedini MR, Qiu Q, Yan X, Tsang BK (2004) Possible role of FLICE-like inhibitory protein (FLIP) in chemoresistant ovarian cancer cells in vitro. Oncogene 23:6997–7004
Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW (2002) Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 9:423–432
Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326
Alexandre J, Batteux F, Nicco C, Chereau C, Laurent A, Guillevin L, Weill B, Goldwasser F (2006) Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo. Int J Cancer 119:41–48
Antonsson B, Montessuit S, Sanchez B, Martinou JC (2001) Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J Biol Chem 276:11615–11623
Arkin M (2005) Protein-protein interactions and cancer: small molecules going in for the kill. Curr Opin Chem Biol 9:317–324
Aronis A, Melendez JA, Golan O, Shilo S, Dicter N, Tirosh O (2003) Potentiation of Fas-mediated apoptosis by attenuated production of mitochondria-derived reactive oxygen species. Cell Death Differ 10:335–344
Azad N, Vallyathan V, Wang L, Tantishaiyakul V, Stehlik C, Leonard SS, Rojanasakul Y (2006) S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis. J Biol Chem 281:34124–34134
Azad N, Iyer AK, Manosroi A, Wang L, Rojanasakul Y (2008a) Superoxide-mediated proteasomal degradation of Bcl-2 determines cell susceptibility to Cr(VI)-induced apoptosis. Carcinogenesis 29:1538–1545
Azad N, Rojanasakul Y, Vallyathan V (2008b) Inflammation and lung cancer: roles of reactive oxygen/nitrogen species. J Toxicol Environ Health B Crit Rev 11:1–15
Azad N, Iyer A, Vallyathan V, Wang L, Castranova V, Stehlik C, Rojanasakul Y (2010) Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation. Ann N Y Acad Sci 1203:1–6
Barbouti A, Amorgianiotis C, Kolettas E, Kanavaros P, Galaris D (2007) Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radic Biol Med 43:1377–1387
Barnhart BC, Alappat EC, Peter ME (2003) The CD95 type I/type II model. Semin Immunol 15:185–193
Bernardi P, Scorrano L, Colonna R, Petronilli V, Di Lisa F (1999) Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur J Biochem 264:687–701
Boldin MP, Varfolomeev EE, Pancer Z, Mett IL, Camonis JH, Wallach D (1995) A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem 270:7795–7798
Borutaite V, Brown GC (2001) Caspases are reversibly inactivated by hydrogen peroxide. FEBS Lett 500:114–118
Borutaite V, Brown GC (2003) Nitric oxide induces apoptosis via hydrogen peroxide, but necrosis via energy and thiol depletion. Free Radic Biol Med 35:1457–1468
Bratton SB, MacFarlane M, Cain K, Cohen GM (2000) Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp Cell Res 256:27–33
Brown GC, Borutaite V (2008) Regulation of apoptosis by the redox state of cytochrome c. Biochim Biophys Acta 1777:877–881
Buolamwini JK (1999) Novel anticancer drug discovery. Curr Opin Chem Biol 3:500–509
Cerretani D, Bello S, Cantatore S, Fiaschi AI, Montefrancesco G, Neri M, Pomara C, Riezzo I, Fiore C, Bonsignore A, Turillazzi E, Fineschi V (2011) Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFalpha-mediated apoptosis in rat liver. Pharmacol Res 64:517–527
Chang DJ, Ringold GM, Heller RA (1992) Cell killing and induction of manganous superoxide dismutase by tumor necrosis factor-alpha is mediated by lipoxygenase metabolites of arachidonic acid. Biochem Biophys Res Commun 188:538–546
Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S, Peter ME, Yang X (2002) c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J 21:3704–3714
Chanvorachote P, Nimmannit U, Wang L, Stehlik C, Lu B, Azad N, Rojanasakul Y (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
Chanvorachote P, Nimmannit U, Stehlik C, Wang L, Jiang BH, Ongpipatanakul B, Rojanasakul Y (2006) Nitric oxide regulates cell sensitivity to cisplatin-induced apoptosis through S-nitrosylation and inhibition of Bcl-2 ubiquitination. Cancer Res 66:6353–6360
Chen Q, Lesnefsky EJ (2006) Depletion of cardiolipin and cytochrome c during ischemia increases hydrogen peroxide production from the electron transport chain. Free Radic Biol Med 40:976–982
Chen ZX, Pervaiz S (2007) Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells. Cell Death Differ 14:1617–1627
Chen ZX, Pervaiz S (2009) BCL-2: pro-or anti-oxidant? Front Biosci (Elite Ed) 1:263–268
Chen SH, Wu HL, Lin MT, Jen CJ, Wing LY, Lei HY, Tsao CJ, Chang WC (1992) Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced endothelial cell injury. Prostaglandins Leukot Essent Fatty Acids 45:299–305
Chen Z, Jiang H, Wan Y, Bi C, Yuan Y (2011) H(2)O (2)-induced secretion of tumor necrosis factor-alpha evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK. Cytotechnology 64:65–73
Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505–512
Circu ML, Aw TY (2009) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762
Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762
Circu ML, Moyer MP, Harrison L, Aw TY (2009) Contribution of glutathione status to oxidant-induced mitochondrial DNA damage in colonic epithelial cells. Free Radic Biol Med 47:1190–1198
Clement MV, Hirpara JL, Pervaiz S (2003) Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing tumor cells to receptor and drug-induced apoptosis independent of the mitochondria. Cell Death Differ 10:1273–1285
Cook SA, Sugden PH, Clerk A (1999) Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res 85:940–949
Crawford DR, Wang Y, Schools GP, Kochheiser J, Davies KJ (1997) Down-regulation of mammalian mitochondrial RNAs during oxidative stress. Free Radic Biol Med 22:551–559
Crawford DR, Abramova NE, Davies KJ (1998) Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides. Free Radic Biol Med 25:1106–1111
Cross AR, Jones OT (1991) Enzymic mechanisms of superoxide production. Biochim Biophys Acta 1057:281–298
Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219
Day TW, Najafi F, Wu CH, Safa AR (2006) Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis. Biochem Pharmacol 71:1551–1561
Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Antonsson B, Martinou JC (1999) Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 144:891–901
Devadas S, Hinshaw JA, Zaritskaya L, Williams MS (2003) Fas-stimulated generation of reactive oxygen species or exogenous oxidative stress sensitize cells to Fas-mediated apoptosis. Free Radic Biol Med 35:648–661
Eskes R, Desagher S, Antonsson B, Martinou JC (2000) Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol Cell Biol 20:929–935
Fadeel B, Zhivotovsky B, Orrenius S (1999) All along the watchtower: on the regulation of apoptosis regulators. FASEB J 13:1647–1657
Fas SC, Baumann S, Zhu JY, Giaisi M, Treiber MK, Mahlknecht U, Krammer PH, Li-Weber M (2006) Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis. Blood 108:3700–3706
Fesik SW (2005) Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 5:876–885
Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112
Fukazawa T, Fujiwara T, Uno F, Teraishi F, Kadowaki Y, Itoshima T, Takata Y, Kagawa S, Roth JA, Tschopp J, Tanaka N (2001) Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome pathway in p53-mediated apoptosis of human cancer cells. Oncogene 20:5225–5231
Golks A, Brenner D, Krammer PH, Lavrik IN (2006) The c-FLIP-NH2 terminus (p22-FLIP) induces NF-kappaB activation. J Exp Med 203:1295–1305
Goltsev YV, Kovalenko AV, Arnold E, Varfolomeev EE, Brodianskii VM, Wallach D (1997) CASH, a novel caspase homologue with death effector domains. J Biol Chem 272:19641–19644
Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312
Griendling KK, Ushio-Fukai M (2000) Reactive oxygen species as mediators of angiotensin II signaling. Regul Pept 91:21–27
Gulbins E, Welsch J, Lepple-Wienhuis A, Heinle H, Lang F (1997) Inhibition of Fas-induced apoptotic cell death by osmotic cell shrinkage. Biochem Biophys Res Commun 236:517–521
Haldar S, Jena N, Croce CM (1995) Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 92:4507–4511
Hall AG (1999) Review: the role of glutathione in the regulation of apoptosis. Eur J Clin Invest 29:238–245
Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102(Suppl 10):5–12
Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L (1997) MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. Proc Natl Acad Sci USA 94:11333–11338
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Hancock JT, Desikan R, Neill SJ (2001) Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 29:345–350
Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479
Hochstrasser M (1996) Ubiquitin-dependent protein degradation. Annu Rev Genet 30:405–439
Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251
Howard AN, Bridges KA, Meyn RE, Chandra J (2009) ABT-737, a BH3 mimetic, induces glutathione depletion and oxidative stress. Cancer Chemother Pharmacol 65:41–54
Hu S, Vincenz C, Buller M, Dixit VM (1997) A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. J Biol Chem 272:9621–9624
Hu Y, Benedict MA, Wu D, Inohara N, Nunez G (1998) Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc Natl Acad Sci USA 95:4386–4391
Hu H, Jiang C, Schuster T, Li GX, Daniel PT, Lu J (2006) Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of mitochondrial pathway. Mol Cancer Ther 5:1873–1882
Hug H, Enari M, Nagata S (1994) No requirement of reactive oxygen intermediates in Fas-mediated apoptosis. FEBS Lett 351:311–313
Hutchins JB, Barger SW (1998) Why neurons die: cell death in the nervous system. Anat Rec 253:79–90
Inohara N, Koseki T, Hu Y, Chen S, Nunez G (1997) CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proc Natl Acad Sci USA 94:10717–10722
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388:190–195
Iyer AK, Azad N, Talbot S, Stehlik C, Lu B, Wang L, Rojanasakul Y (2011) Antioxidant c-FLIP inhibits Fas ligand-induced NF-kappaB activation in a phosphatidylinositol 3-kinase/Akt-dependent manner. J Immunol 187:3256–3266
Jornot L, Petersen H, Junod AF (1998) Hydrogen peroxide-induced DNA damage is independent of nuclear calcium but dependent on redox-active ions. Biochem J 335(Pt 1):85–94
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661
Kane DJ, Sarafian TA, Anton R, Hahn H, Gralla EB, Valentine JS, Ord T, Bredesen DE (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262:1274–1277
Kataoka T (2005) The caspase-8 modulator c-FLIP. Crit Rev Immunol 25:31–58
Katoh I, Tomimori Y, Ikawa Y, Kurata S (2004) Dimerization and processing of procaspase-9 by redox stress in mitochondria. J Biol Chem 279:15515–15523
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
Kim Y, Suh N, Sporn M, Reed JC (2002) An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 277:22320–22329
Klebanoff SJ (1980) Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med 93:480–489
Kongkaneramit L, Sarisuta N, Azad N, Lu Y, Iyer AK, Wang L, Rojanasakul Y (2008) Dependence of reactive oxygen species and FLICE inhibitory protein on lipofectamine-induced apoptosis in human lung epithelial cells. J Pharmacol Exp Ther 325:969–977
Korsmeyer SJ, McDonnell TJ, Nunez G, Hockenbery D, Young R (1990) Bcl-2: B cell life, death and neoplasia. Curr Top Microbiol Immunol 166:203–207
Kowaltowski AJ, Fiskum G (2005) Redox mechanisms of cytoprotection by Bcl-2. Antioxid Redox Signal 7:508–514
Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795
Kristal BS, Chen J, Yu BP (1994) Sensitivity of mitochondrial transcription to different free radical species. Free Radic Biol Med 16:323–329
Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21:8247–8254
Larrick JW, Wright SC (1990) Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J 4:3215–3223
Lassegue B, Griendling KK (2002) Out phoxing the endothelium: what’s left without p47? Circ Res 90:123–124
LeBlanc HN, Ashkenazi A (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10:66–75
Lee MW, Park SC, Yang YG, Yim SO, Chae HS, Bach JH, Lee HJ, Kim KY, Lee WB, Kim SS (2002) The involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein (MAP) kinase in TRAIL/Apo2L-induced apoptosis. FEBS Lett 512:313–318
Leist M, Jaattela M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589–598
Lenaz G, Bovina C, D’Aurelio M, Fato R, Formiggini G, Genova ML, Giuliano G, Merlo Pich M, Paolucci U, Parenti Castelli G, Ventura B (2002) Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci 959:199–213
Lennon SV, Martin SJ, Cotter TG (1991) Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif 24:203–214
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489
Li D, Ueta E, Kimura T, Yamamoto T, Osaki T (2004) Reactive oxygen species (ROS) control the expression of Bcl-2 family proteins by regulating their phosphorylation and ubiquitination. Cancer Sci 95:644–650
Liston P, Fong WG, Korneluk RG (2003) The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene 22:8568–8580
Lockshin RA, Williams CM (1964) Programmed cell death. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J Insect Physiol 10:643–649
Loeffler M, Kroemer G (2000) The mitochondrion in cell death control: certainties and incognita. Exp Cell Res 256:19–26
Low IC, Chen ZX, Pervaiz S (2010) Bcl-2 modulates resveratrol-induced ROS production by regulating mitochondrial respiration in tumor cells. Antioxid Redox Signal 13:807–819
Malorni W, Rivabene R, Santini MT, Donelli G (1993) N-acetylcysteine inhibits apoptosis and decreases viral particles in HIV-chronically infected U937 cells. FEBS Lett 327:75–78
Mates JM, Sanchez-Jimenez FM (2000) Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol 32:157–170
Matsuda T, Eccleston CA, Rubinstein I, Rennard SI, Joyner WL (1991) Antioxidants attenuate endotoxin-induced microvascular leakage of macromolecules in vivo. J Appl Physiol 70:1483–1489
Mayer M, Noble M (1994) N-acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro. Proc Natl Acad Sci USA 91:7496–7500
Medan D, Wang L, Toledo D, Lu B, Stehlik C, Jiang BH, Shi X, Rojanasakul Y (2005) Regulation of Fas (CD95)-induced apoptotic and necrotic cell death by reactive oxygen species in macrophages. J Cell Physiol 203:78–84
Medema JP, de Jong J, van Hall T, Melief CJ, Offringa R (1999) Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J Exp Med 190:1033–1038
Meier P, Finch A, Evan G (2000) Apoptosis in development. Nature 407:796–801
Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grutter MG (2002) The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem 277:45162–45171
Mikhailov V, Mikhailova M, Pulkrabek DJ, Dong Z, Venkatachalam MA, Saikumar P (2001) Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem 276:18361–18374
Moriishi K, Huang DCS, Cory S, Adams JM (1999) Bcl-2 family members do not inhibit apoptosis by binding the caspase activator Apaf-1. PNAS 96:9683–9688
Moungjaroen J, Nimmannit U, Callery PS, Wang L, Azad N, Lipipun V, Chanvorachote P, Rojanasakul Y (2006) Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation. J Pharmacol Exp Ther 319:1062–1069
Murphy KM, Ranganathan V, Farnsworth ML, Kavallaris M, Lock RB (2000) Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ 7:102–111
Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM (1998) An induced proximity model for caspase-8 activation. J Biol Chem 273:2926–2930
Naismith JH, Sprang SR (1998) Modularity in the TNF-receptor family. Trends Biochem Sci 23:74–79
Nakajima T, Takayama T, Miyanishi K, Nobuoka A, Hayashi T, Abe T, Kato J, Sakon K, Naniwa Y, Tanabe H, Niitsu Y (2003) Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione S-transferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-D-phenylglycine ethylester. J Pharmacol Exp Ther 306:861–869
Nicholson DW (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6:1028–1042
Nicholson DW, Thornberry NA (1997) Caspases: killer proteases. Trends Biochem Sci 22:299–306
Nitobe J, Yamaguchi S, Okuyama M, Nozaki N, Sata M, Miyamoto T, Takeishi Y, Kubota I, Tomoike H (2003) Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes. Cardiovasc Res 57:119–128
Oh SH, Lim SC (2006) A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicol Appl Pharmacol 212:212–223
Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619
Osford SM, Dallman CL, Johnson PW, Ganesan A, Packham G (2004) Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells. Curr Med Chem 11:1031–1039
Pan G, O’Rourke K, Dixit VM (1998) Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J Biol Chem 273:5841–5845
Perez D, White E (2003) E1A sensitizes cells to tumor necrosis factor alpha by downregulating c-FLIP S. J Virol 77:2651–2662
Pervaiz S, Clement MV (2002) A permissive apoptotic environment: function of a decrease in intracellular superoxide anion and cytosolic acidification. Biochem Biophys Res Commun 290:1145–1150
Peter ME (2004) The flip side of FLIP. Biochem J 382:e1–e3
Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K, Jayawardena S, De Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G (2004) Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119:529–542
Rachek LI, Yuzefovych LV, Ledoux SP, Julie NL, Wilson GL (2009) Troglitazone, but not rosiglitazone, damages mitochondrial DNA and induces mitochondrial dysfunction and cell death in human hepatocytes. Toxicol Appl Pharmacol 240:348–354
Rasper DM, Vaillancourt JP, Hadano S, Houtzager VM, Seiden I, Keen SL, Tawa P, Xanthoudakis S, Nasir J, Martindale D, Koop BF, Peterson EP, Thornberry NA, Huang J, MacPherson DP, Black SC, Hornung F, Lenardo MJ, Hayden MR, Roy S, Nicholson DW (1998) Cell death attenuation by ‘Usurpin’, a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell Death Differ 5:271–288
Reed JC (1997) Cytochrome c: can’t live with it–can’t live without it. Cell 91:559–562
Reed JC, Pellecchia M (2005) Apoptosis-based therapies for hematologic malignancies. Blood 106:408–418
Reinehr R, Becker S, Eberle A, Grether-Beck S, Haussinger D (2005) Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. J Biol Chem 280:27179–27194
Ricci C, Pastukh V, Leonard J, Turrens J, Wilson G, Schaffer D, Schaffer SW (2008) Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am J Physiol Cell Physiol 294:C413–C422
Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, Choi AM (2007) Mechanisms of cell death in oxidative stress. Antioxid Redox Signal 9:49–89
Salvesen GS, Dixit VM (1997) Caspases: intracellular signaling by proteolysis. Cell 91:443–446
Santamaria G, Martinez-Diez M, Fabregat I, Cuezva JM (2006) Efficient execution of cell death in non-glycolytic cells requires the generation of ROS controlled by the activity of mitochondrial H + -ATP synthase. Carcinogenesis 27:925–935
Sato T, Machida T, Takahashi S, Iyama S, Sato Y, Kuribayashi K, Takada K, Oku T, Kawano Y, Okamoto T, Takimoto R, Matsunaga T, Takayama T, Takahashi M, Kato J, Niitsu Y (2004) Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells. J Immunol 173:285–296
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 17:1675–1687
Scaffidi C, Schmitz I, Krammer PH, Peter ME (1999) The role of c-FLIP in modulation of CD95-induced apoptosis. J Biol Chem 274:1541–1548
Shacter E, Weitzman SA (2002) Chronic inflammation and cancer. Oncology (Williston Park) 16:217–226, 229; discussion 230–232
Shi Y (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9:459–470
Shu HB, Halpin DR, Goeddel DV (1997) Casper is a FADD- and caspase-related inducer of apoptosis. Immunity 6:751–763
Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5:415–418
Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ (1999) Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144:281–292
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446
Tanaka T, Yoshimi M, Maeyama T, Hagimoto N, Kuwano K, Hara N (2002) Resistance to Fas-mediated apoptosis in human lung fibroblast. Eur Respir J 20:359–368
Tang H, Qin Y, Li J, Gong X (2011) The scavenging of superoxide radicals promotes apoptosis induced by a novel cell-permeable fusion protein, sTRAIL: FeSOD, in tumor necrosis factor-related apoptosis-inducing ligand-resistant leukemia cells. BMC Biol 9:18
Taniyama Y, Griendling KK (2003) Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 42:1075–1081
Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517–521
Tschopp J, Irmler M, Thome M (1998) Inhibition of fas death signals by FLIPs. Curr Opin Immunol 10:552–558
Tsujimoto Y, Shimizu S (2000) VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ 7:1174–1181
Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226:1097–1099
Van Houten B, Woshner V, Santos JH (2006) Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst) 5:145–152
Vaux DL, Korsmeyer SJ (1999) Cell death in development. Cell 96:245–254
Ventura JJ, Cogswell P, Flavell RA, Baldwin AS Jr, Davis RJ (2004) JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species. Genes Dev 18:2905–2915
Vercammen D, Brouckaert G, Denecker G, Van de Craen M, Declercq W, Fiers W, Vandenabeele P (1998) Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med 188:919–930
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53
Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP (1999) Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331–367
Wang L, Azad N, Kongkaneramit L, Chen F, Lu Y, Jiang BH, Rojanasakul Y (2008) The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol 180:3072–3080
Wenzel U, Kuntz S, De Sousa UJ, Daniel H (2003) Nitric oxide suppresses apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Int J Cancer 106:666–675
Wong GH (1995) Protective roles of cytokines against radiation: induction of mitochondrial MnSOD. Biochim Biophys Acta 1271:205–209
Wong GH, Elwell JH, Oberley LW, Goeddel DV (1989) Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 58:923–931
Wu LL, Chiou CC, Chang PY, Wu JT (2004) Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta 339:1–9
Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306
Yang JK (2008) FLIP as an anti-cancer therapeutic target. Yonsei Med J 49:19–27
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:1129–1132
Yuan J (1997) Transducing signals of life and death. Curr Opin Cell Biol 9:247–251
Zalba G, San Jose G, Moreno MU, Fortuno MA, Fortuno A, Beaumont FJ, Diez J (2001) Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 38:1395–1399
Zuzarte-Luis V, Hurle JM (2002) Programmed cell death in the developing limb. Int J Dev Biol 46:871–876
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Azad, N., Iyer, A.K.V. (2014). Reactive Oxygen Species and Apoptosis. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_15
Download citation
DOI: https://doi.org/10.1007/978-3-642-30018-9_15
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-30017-2
Online ISBN: 978-3-642-30018-9
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences