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Reactive Oxygen Species in Cell Fate Decisions

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Essentials of Apoptosis

Abstract

Redox homeostasis is a function of the balance between the intracellular generation of reactive oxygen species (ROS) and the cellular antioxidant defense systems. Therefore, the degree of oxidative stress is a direct outcome of the rate at which the cells’ metabolic processes fuel ROS production and the efficiency with which the antioxidant machinery is able to deal with the impending accumulation. Invariably, the rate of ROS production outweighs the rate of detoxification, thereby leading to excessive accumulation of ROS, manifested as oxidative stress. Although the cellular processes involved in ROS generation, the antioxidant defense mechanisms, and the chemistry of the various redox reactions have all been well described for years, the last couple of decades have seen an enormous increase in activity around the biological relevance of ROS during physiological as well as pathological settings. These studies have highlighted the direct involvement of ROS generated from intracellular sources, such as the NADPH oxidase and/or mitochondrial electron transport chain, in a variety of models of cell death signaling. Many novel targets of ROS have been identified, and their biological relevance is beginning to be unraveled. Whiles a large body of evidence has corroborated the association between elevated ROS and cell death signaling, there is also an emerging notion that at relatively low levels, ROS function as signaling molecules to promote cellular proliferation and growth. This chapter aims to review the current state of our understanding of the cellular sources of ROS as well as the involvement of ROS in cell fate signaling.

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References

  1. Halliwell B, Cross CE. Oxygen-derived species: Their relation to human disease and environmental stress. Environ Health Perspect 1994;102(Suppl 10):5–12.

    Article  PubMed  CAS  Google Scholar 

  2. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527–605.

    PubMed  CAS  Google Scholar 

  3. Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47–95.

    PubMed  CAS  Google Scholar 

  4. Filomeni G, Ciriolo MR. Redox control of apoptosis: An update. Antioxid Redox Signal 2006;8:2187–92.

    Article  PubMed  CAS  Google Scholar 

  5. Fruehauf JP, Meyskens FL, Jr. Reactive oxygen species: A breath of life or death? Clin Cancer Res 2007;13:789–94.

    Article  PubMed  CAS  Google Scholar 

  6. Orrenius S. Reactive oxygen species in mitochondria-mediated cell death. Drug Metab Rev 2007;39:443–55.

    Article  PubMed  CAS  Google Scholar 

  7. Ryter SW, Kim HP, Hoetzel A, et al. Mechanisms of cell death in oxidative stress. Antioxid Redox Signal 2007;9:49–89.

    Article  PubMed  CAS  Google Scholar 

  8. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 2004;4:181–9.

    Article  PubMed  CAS  Google Scholar 

  9. Reinehr R, Becker S, Eberle A, Grether-Beck S, Haussinger D. Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. J Biol Chem 2005;280:27179–94.

    Article  PubMed  CAS  Google Scholar 

  10. Zhang S, Lin Y, Kim YS, Hande MP, Liu ZG, Shen HM. c-Jun N-terminal kinase mediates hydrogen peroxide-induced cell death via sustained poly(ADP-ribose) polymerase-1 activation. Cell Death Differ 2007;14:1001–10.

    Article  PubMed  CAS  Google Scholar 

  11. Hiraoka W, Vazquez N, Nieves-Neira W, Chanock SJ, Pommier Y. Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells. J Clin Invest 1998;102:1961–8.

    Article  PubMed  CAS  Google Scholar 

  12. Tammariello SP, Quinn MT, Estus S. NADPH oxidase contributes directly to oxidative stress and apoptosis in nerve growth factor-deprived sympathetic neurons. J Neurosci 2000;20:RC53.

    PubMed  CAS  Google Scholar 

  13. Raha S, Robinson BH. Mitochondria, oxygen free radicals, and apoptosis. Am J Med Genet 2001;106:62–70.

    Article  PubMed  CAS  Google Scholar 

  14. Orrenius S, Gogvadze V, Zhivotovsky B. Mitochondrial oxidative stress: Implications for cell death. Annu Rev Pharmacol Toxicol 2007;47:143–83.

    Article  PubMed  CAS  Google Scholar 

  15. Ricci JE, Munoz-Pinedo C, Fitzgerald P, et al. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell 2004;117:773–86.

    Article  PubMed  CAS  Google Scholar 

  16. Chandel NS, Schumacker PT, Arch RH. Reactive oxygen species are downstream products of TRAF-mediated signal transduction. J Biol Chem 2001;276:42728–36.

    Article  PubMed  CAS  Google Scholar 

  17. Ventura JJ, Cogswell P, Flavell RA, Baldwin AS, Jr., Davis RJ. JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species. Genes Dev 2004;18:2905–15.

    Article  PubMed  CAS  Google Scholar 

  18. Lin Y, Choksi S, Shen HM, et al. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem 2004;279:10822–8.

    Article  PubMed  CAS  Google Scholar 

  19. Hirpara JL, Clement MV, Pervaiz S. Intracellular acidification triggered by mitochondrial-derived hydrogen peroxide is an effector mechanism for drug-induced apoptosis in tumor cells. J Biol Chem 2001;276:514–21.

    Article  PubMed  CAS  Google Scholar 

  20. Narita M, Shimizu S, Ito T, et al. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci USA 1998;95:14681–6.

    Article  PubMed  CAS  Google Scholar 

  21. Bustamante J, Nutt L, Orrenius S, Gogvadze V. Arsenic stimulates release of cytochrome c from isolated mitochondria via induction of mitochondrial permeability transition. Toxicol Appl Pharmacol 2005;207:110–6.

    Article  PubMed  CAS  Google Scholar 

  22. Tuominen EK, Wallace CJ, Kinnunen PK. Phospholipid-cytochrome c interaction: Evidence for the extended lipid anchorage. J Biol Chem 2002;277:8822–6.

    Article  PubMed  CAS  Google Scholar 

  23. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S. Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci USA 2002;99:1259–63.

    Article  PubMed  CAS  Google Scholar 

  24. Manna SK, Zhang HJ, Yan T, Oberley LW, Aggarwal BB. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J Biol Chem 1998;273:13245–54.

    Article  PubMed  CAS  Google Scholar 

  25. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997;389:300–5.

    Article  PubMed  CAS  Google Scholar 

  26. Kagan VE, Tyurin VA, Jiang J, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 2005;1:223–32.

    Article  PubMed  CAS  Google Scholar 

  27. Migliaccio E, Giorgio M, Pelicci PG. Apoptosis and aging: Role of p66Shc redox protein. Antioxid Redox Signal 2006;8:600–8.

    Article  PubMed  CAS  Google Scholar 

  28. Giorgio M, Migliaccio E, Orsini F, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 2005;122:221–33.

    Article  PubMed  CAS  Google Scholar 

  29. Pinton P, Rimessi A, Marchi S, et al. Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 2007;315:659–63.

    Article  PubMed  CAS  Google Scholar 

  30. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001;11:372–7.

    Article  PubMed  CAS  Google Scholar 

  31. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003;10:45–65.

    Article  PubMed  CAS  Google Scholar 

  32. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003;114:181–90.

    Article  PubMed  CAS  Google Scholar 

  33. Shakibaei M, Schulze-Tanzil G, Takada Y, Aggarwal BB. Redox regulation of apoptosis by members of the TNF superfamily. Antioxid Redox Signal 2005;7:482–96.

    Article  PubMed  CAS  Google Scholar 

  34. Shen HM, Pervaiz S. TNF receptor superfamily-induced cell death: Redox-dependent execution. FASEB J 2006;20:1589–98.

    Article  PubMed  CAS  Google Scholar 

  35. Chovolou Y, Watjen W, Kampkotter A, Kahl R. Resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in rat hepatoma cells expressing TNF-alpha is linked to low antioxidant enzyme expression. J Biol Chem 2003;278:29626–32.

    Article  PubMed  CAS  Google Scholar 

  36. Hughes G, Murphy MP, Ledgerwood EC. Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor kappaB to modulate tumour necrosis factor-induced apoptosis: Evidence from mitochondria-targeted antioxidants. Biochem J 2005;389:83–9.

    Article  PubMed  CAS  Google Scholar 

  37. Deshpande SS, Angkeow P, Huang J, Ozaki M, Irani K. Rac1 inhibits TNF-alpha-induced endothelial cell apoptosis: Dual regulation by reactive oxygen species. FASEB J 2000;14:1705–14.

    Google Scholar 

  38. Nagata S. Fas ligand-induced apoptosis. Annu Rev Genet 1999;33:29–55.

    Article  PubMed  CAS  Google Scholar 

  39. Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003;10:26–35.

    Article  PubMed  CAS  Google Scholar 

  40. Devadas S, Hinshaw JA, Zaritskaya L, Williams MS. Fas-stimulated generation of reactive oxygen species or exogenous oxidative stress sensitizes cells to Fas-mediated apoptosis. Free Radic Biol Med 2003;35:648–61.

    Article  PubMed  CAS  Google Scholar 

  41. Sato T, Machida T, Takahashi S, et al. Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells. J Immunol 2004;173:285–96.

    PubMed  CAS  Google Scholar 

  42. Malassagne B, Ferret PJ, Hammoud R, et al. The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse. Gastroenterology 2001;121:1451–9.

    Article  PubMed  CAS  Google Scholar 

  43. Minana JB, Gomez-Cambronero L, Lloret A, et al. Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism. Hepatology 2002;35:1205–14.

    Article  PubMed  CAS  Google Scholar 

  44. Denning TL, Takaishi H, Crowe SE, Boldogh I, Jevnikar A, Ernst PB. Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Radic Biol Med 2002;33:1641–50.

    Article  PubMed  CAS  Google Scholar 

  45. Wang S, El-Deiry WS. TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 2003;22:8628–33.

    Article  PubMed  CAS  Google Scholar 

  46. Izeradjene K, Douglas L, Tillman DM, Delaney AB, Houghton JA. Reactive oxygen species regulate caspase activation in tumor necrosis factor-related apoptosis-inducing ligand-resistant human colon carcinoma cell lines. Cancer Res 2005;65:7436–45.

    Article  PubMed  CAS  Google Scholar 

  47. Hao JH, Yu M, Liu FT, Newland AC, Jia L. Bcl-2 inhibitors sensitize tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by uncoupling of mitochondrial respiration in human leukemic CEM cells. Cancer Res 2004;64:3607–16.

    Article  PubMed  CAS  Google Scholar 

  48. Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK. Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis 2005;26:1905–13.

    Article  PubMed  CAS  Google Scholar 

  49. Kim H, Kim EH, Eom YW, et al. Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of DR5. Cancer Res 2006;66:1740–50.

    Article  PubMed  CAS  Google Scholar 

  50. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000;103:239–52.

    Article  PubMed  CAS  Google Scholar 

  51. Shen HM, Liu ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 2006;40:928–39.

    Article  PubMed  CAS  Google Scholar 

  52. Saitoh M, Nishitoh H, Fujii M, et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 1998;17:2596–606.

    Article  PubMed  CAS  Google Scholar 

  53. Yoshizumi M, Abe J, Haendeler J, Huang Q, Berk BC. Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species. J Biol Chem 2000;275:11706–12.

    Article  PubMed  CAS  Google Scholar 

  54. Wang T, Arifoglu P, Ronai Z, Tew KD. Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus. J Biol Chem 2001;276:20999–1003.

    Article  PubMed  CAS  Google Scholar 

  55. Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 2005;120:649–61.

    Article  PubMed  CAS  Google Scholar 

  56. Tobiume K, Matsuzawa A, Takahashi T, et al. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2001;2:222–8.

    Article  PubMed  CAS  Google Scholar 

  57. Li Y, Arita Y, Koo HC, Davis JM, Kazzaz JA. Inhibition of c-Jun N-terminal kinase pathway improves cell viability in response to oxidant injury. Am J Respir Cell Mol Biol 2003;29:779–83.

    Article  PubMed  CAS  Google Scholar 

  58. Wu YT, Zhang S, Kim YS, et al. Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death. Cell Death Differ 2008;15:386–97.

    Article  PubMed  CAS  Google Scholar 

  59. Shen HM, Lin Y, Choksi S, et al. Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Mol Cell Biol 2004;24:5914–22.

    Article  PubMed  CAS  Google Scholar 

  60. Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 2000;288:870–4.

    Article  PubMed  CAS  Google Scholar 

  61. Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999;19:8469–78.

    PubMed  CAS  Google Scholar 

  62. Inoshita S, Takeda K, Hatai T, et al. Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress. J Biol Chem 2002;277:43730–4.

    Article  PubMed  CAS  Google Scholar 

  63. Lei K, Nimnual A, Zong WX, et al. The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol Cell Biol 2002;22:4929–42.

    Article  PubMed  CAS  Google Scholar 

  64. Lei K, Davis RJ. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA 2003;100:2432–7.

    Article  PubMed  CAS  Google Scholar 

  65. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004;18:2195–224.

    Article  PubMed  CAS  Google Scholar 

  66. Piette J, Piret B, Bonizzi G, et al. Multiple redox regulation in NF-kappaB transcription factor activation. Biol Chem 1997;378:1237–45.

    PubMed  CAS  Google Scholar 

  67. Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: Fifteen years later. Biochem Pharmacol 2006;72:1493–505.

    Article  PubMed  CAS  Google Scholar 

  68. Pantano C, Reynaert NL, van der Vliet A, Janssen-Heininger YM. Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway. Antioxid Redox Signal 2006;8:1791–806.

    Article  PubMed  CAS  Google Scholar 

  69. Byun MS, Jeon KI, Choi JW, Shim JY, Jue DM. Dual effect of oxidative stress on NF-kappakB activation in HeLa cells. Exp Mol Med 2002;34:332–9.

    Article  PubMed  CAS  Google Scholar 

  70. Korn SH, Wouters EF, Vos N, Janssen-Heininger YM. Cytokine-induced activation of nuclear factor-kappa B is inhibited by hydrogen peroxide through oxidative inactivation of IkappaB kinase. J Biol Chem 2001;276:35693–700.

    Article  PubMed  CAS  Google Scholar 

  71. Hayakawa M, Miyashita H, Sakamoto I, et al. Evidence that reactive oxygen species do not mediate NF-kappaB activation. EMBO J 2003;22:3356–66.

    Article  PubMed  CAS  Google Scholar 

  72. De Smaele E, Zazzeroni F, Papa S, et al. Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 2001;414:308–13.

    Article  PubMed  Google Scholar 

  73. Tang G, Minemoto Y, Dibling B, et al. Inhibition of JNK activation through NF-kappaB target genes. Nature 2001;414:313–7.

    Article  PubMed  CAS  Google Scholar 

  74. Pham CG, Bubici C, Zazzeroni F, et al. Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 2004;119:529–42.

    Article  PubMed  CAS  Google Scholar 

  75. Papa S, Bubici C, Zazzeroni F, et al. The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease. Cell Death Differ 2006;13:712–29.

    Article  PubMed  CAS  Google Scholar 

  76. Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X, Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ 2006;13:730–7.

    Article  PubMed  CAS  Google Scholar 

  77. Liu J, Yang D, Minemoto Y, Leitges M, Rosner MR, Lin A. NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta. Mol Cell 2006;21:467–80.

    Article  PubMed  CAS  Google Scholar 

  78. Benhar M, Dalyot I, Engelberg D, Levitzki A. Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress. Mol Cell Biol 2001;21:6913–26.

    Article  PubMed  CAS  Google Scholar 

  79. Nakajima A, Kojima Y, Nakayama M, Yagita H, Okumura K, Nakano H. Downregulation of c-FLIP promotes caspase-dependent JNK activation and reactive oxygen species accumulation in tumor cells. Oncogene 2008;27:76–84.

    Article  PubMed  CAS  Google Scholar 

  80. Burdon RH, Gill V, Rice-Evans C. Cell proliferation and oxidative stress. Free Radic Res Commun 1989;7:149–59.

    Article  PubMed  CAS  Google Scholar 

  81. Burdon RH. Control of cell proliferation by reactive oxygen species. Biochem Soc Trans 1996;24:1028–32.

    PubMed  CAS  Google Scholar 

  82. Burdon RH. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 1995;18:775–94.

    Article  PubMed  CAS  Google Scholar 

  83. Sauer H, Wartenberg M, Hescheler J. Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell Physiol Biochem 2001;11:173–86.

    Article  PubMed  CAS  Google Scholar 

  84. Droge W, Eck HP, Mihm S. HIV-induced cysteine deficiency and T-cell dysfunction—A rationale for treatment with N-acetylcysteine. Immunol Today 1992;13:211–4.

    Article  PubMed  CAS  Google Scholar 

  85. Shibanuma M, Kuroki T, Nose K. Superoxide as a signal for increase in intracellular pH. J Cell Physiol 1988;136:379–83.

    Article  PubMed  CAS  Google Scholar 

  86. Cullen JJ, Weydert C, Hinkhouse MM, et al. The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. Cancer Res 2003;63:1297–303.

    PubMed  CAS  Google Scholar 

  87. Oberley LW. Anticancer therapy by overexpression of superoxide dismutase. Antioxid Redox Signal 2001;3:461–72.

    Article  PubMed  CAS  Google Scholar 

  88. Weydert C, Roling B, Liu J, et al. Suppression of the malignant phenotype in human pancreatic cancer cells by the overexpression of manganese superoxide dismutase. Mol Cancer Ther 2003;2:361–9.

    PubMed  CAS  Google Scholar 

  89. Zhao Y, Xue Y, Oberley TD, et al. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Cancer Res 2001;61:6082–8.

    PubMed  CAS  Google Scholar 

  90. Darby Weydert CJ, Smith BB, Xu L, et al. Inhibition of oral cancer cell growth by adenovirus MnSOD plus BCNU treatment. Free Radic Biol Med 2003;34:316–29.

    Article  PubMed  CAS  Google Scholar 

  91. Qin S, Chock PB. Implication of phosphatidylinositol 3-kinase membrane recruitment in hydrogen peroxide-induced activation of PI3K and Akt. Biochemistry 2003;42:2995–3003.

    Article  PubMed  CAS  Google Scholar 

  92. Irani K, Xia Y, Zweier JL, et al. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 1997;275:1649–52.

    Google Scholar 

  93. Pervaiz S, Cao J, Chao OS, Chin YY, Clement MV. Activation of the RacGTPase inhibits apoptosis in human tumor cells. Oncogene 2001;20:6263–8.

    Article  PubMed  CAS  Google Scholar 

  94. Suh YA, Arnold RS, Lassegue B, et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature 1999;401:79–82.

    Google Scholar 

  95. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994;15:7–10.

    Article  PubMed  CAS  Google Scholar 

  96. Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature 1993;361:365–9.

    Article  PubMed  CAS  Google Scholar 

  97. Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H, Tsujimoto Y. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature 1995;374:811–3.

    Article  PubMed  CAS  Google Scholar 

  98. Clement MV, Stamenkovic I. Superoxide anion is a natural inhibitor of FAS-mediated cell death. EMBO J 1996;15:216–25.

    PubMed  CAS  Google Scholar 

  99. Hampton MB, Orrenius S. Dual regulation of caspase activity by hydrogen peroxide: Implications for apoptosis. FEBS Lett 1997;414:552–6.

    Article  PubMed  CAS  Google Scholar 

  100. Mannick JB, Miao XQ, Stamler JS. Nitric oxide inhibits Fas-induced apoptosis. J Biol Chem 1997;272:24125–8.

    Article  PubMed  CAS  Google Scholar 

  101. Pervaiz S, Ramalingam JK, Hirpara JL, Clement MV. Superoxide anion inhibits drug-induced tumor cell death. FEBS Lett 1999;459:343–8.

    Article  PubMed  CAS  Google Scholar 

  102. Hockenbery D, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993;75:241–51.

    Article  PubMed  CAS  Google Scholar 

  103. Hampton MB, Fadeel B, Orrenius S. Redox regulation of the caspases during apoptosis. Ann NY Acad Sci 1998;854:328–35.

    Article  PubMed  CAS  Google Scholar 

  104. Clement MV, Pervaiz S. Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: A hypothesis. Free Radic Res 1999;30:247–52.

    Article  PubMed  CAS  Google Scholar 

  105. Clement MV, Pervaiz S. Intracellular superoxide and hydrogen peroxide concentrations: A critical balance that determines survival or death. Redox Rep 2001;6:211–4.

    Article  PubMed  CAS  Google Scholar 

  106. Clement MV, Hirpara JL, Pervaiz S. Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing tumor cells to receptor and drug-induced apoptosis independent of the mitochondria. Cell Death Differ 2003;10:1273–85.

    Article  PubMed  CAS  Google Scholar 

  107. Lin KI, Pasinelli P, Brown RH, Hardwick JM, Ratan RR. Decreased intracellular superoxide levels activate Sindbis virus-induced apoptosis. J Biol Chem 1999;274:13650–5.

    Article  PubMed  CAS  Google Scholar 

  108. Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol 1990;186:1–85.

    Article  PubMed  CAS  Google Scholar 

  109. Clement MV, Hirpara JL, Chawdhury SH, Pervaiz S. Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood 1998;92:996–1002.

    PubMed  CAS  Google Scholar 

  110. Pervaiz S, Clement MV. A permissive apoptotic environment: Function of a decrease in intracellular superoxide anion and cytosolic acidification. Biochem Biophys Res Commun 2002;290:1145–50.

    Article  PubMed  CAS  Google Scholar 

  111. Nicholson DW, All A, Thornberry NA, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 1995;376:37–43.

    Article  PubMed  CAS  Google Scholar 

  112. Thornberry NA. Caspases: Key mediators of apoptosis. Chem Biol 1998;5:97–103.

    Article  Google Scholar 

  113. Thorneberry NA. Interleukine-1-b converting enzyme. Methods Enzymol 1994;244:615–31.

    Article  Google Scholar 

  114. Mannick JB, Hausladen A, Liu L, et al. Fas-induced caspase denitrosylation. Science 1999;284:651–4.

    Article  PubMed  CAS  Google Scholar 

  115. Yamakawa H, Ito Y, Naganawa T, et al. Activation of caspase-9 and -3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation. Neurol Res 2000;22:556–64.

    PubMed  CAS  Google Scholar 

  116. Shimizu S, Eguchi Y, Kamiike W, et al. Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux. Proc Natl Acad Sci USA 1998;95:1455–9.

    Article  PubMed  CAS  Google Scholar 

  117. Akram S, Teong HF, Fliegel L, Pervaiz S, Clement MV. Reactive oxygen species-mediated regulation of the Na+-H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers. Cell Death Differ 2006;13:628–41.

    Article  PubMed  CAS  Google Scholar 

  118. Ahmad KA, Iskandar KB, Hirpara JL, Clement MV, Pervaiz S. Hydrogen peroxide-mediated cytosolic acidification is a signal for mitochondrial translocation of Bax during drug-induced apoptosis of tumor cells. Cancer Res 2004;64:7867–78.

    Article  PubMed  CAS  Google Scholar 

  119. Chao DT, Korsmeyer SJ. BCL-2 family: Regulators of cell death. Annu Rev Immunol 1998;16:395–419.

    Google Scholar 

  120. Allsopp TE, Wyatt S, Paterson HF, Davies AM. The proto-oncogene Bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 1993;73:295–307.

    Article  PubMed  CAS  Google Scholar 

  121. Garcia I, Martinou I, Tsujimotot Y, Martinou JC. Prevention of programmed cell death of sympathetic neurons by the Bcl-2 proto-oncogene. Science 1992;258:302–4.

    Article  PubMed  CAS  Google Scholar 

  122. Nunez G, London L, Hockenbery D, Alexander M, McKearn JP, Korsmeyer SJ. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor deprived hematopoietic cell lines. J Immunol 1990;144:3602–10.

    PubMed  CAS  Google Scholar 

  123. Chen ZX, Pervaiz S. Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells. Cell Death Differ 2007;14:1617–27.

    Google Scholar 

  124. Thangaraju M, Sharma K, Liu D, Shen SH, Srikant CB. Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. Cancer Res 1999;59:1649–54.

    PubMed  CAS  Google Scholar 

  125. Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH: Early events that modulate caspase activation during apoptosis. Nat Cell Biol 2000;2:318–25.

    Article  PubMed  CAS  Google Scholar 

  126. Cardone RA, Casavola V, Reshkin SJ. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat Rev Cancer 2005;5:786–95.

    Article  PubMed  CAS  Google Scholar 

  127. Gillies RJ, Raghunand N, Karczmar GS, Bhujwalla ZM. MRI of the tumor microenvironment. J Magn Reson Imaging 2002;16:430–50.

    Article  PubMed  Google Scholar 

  128. Montcourrier P, Silver I, Farnoud R, Bird I, Rochefort H. Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. Clin Exp Metastasis 1997;15:382–92.

    Article  PubMed  CAS  Google Scholar 

  129. Hagag N, Lacal JC, Graber M, Aaronson S, Viola MV. Microinjection of ras p21 induces a rapid rise in intracellular pH. Mol Cell Biol 1987;7:1984–8.

    PubMed  CAS  Google Scholar 

  130. Akram S, Teong HF, Fliegel L, Pervaiz S, Clement MV. Reactive oxygen species-mediated regulation of the Na(+)-H(+) exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers. Cell Death Differ 2006;13:628–41.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are supported by research grants from the National Medical Research Council, Singapore, Biomedical Research Council, Singapore, Ministry of Education Research Funds, and Singapore Cancer Syndicate.

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Correspondence to Han-Ming Shen .

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Shen, HM., Pervaiz, S. (2009). Reactive Oxygen Species in Cell Fate Decisions. In: Dong, Z., Yin, XM. (eds) Essentials of Apoptosis. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-381-7_8

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