Abstract
Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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Simon HU, Yousefi S, Schranz C, Schapowal A, Bachert C, Blaser K. Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J Immunol 1997; 158: 3902–3908.
Dibbert B, Weber M, Nikolaizik WH, et al. Cytokinemediated Bax deficiency and consequent delayed neutrophil apoptosis: A general mechanism to accumulate effector cells in inflammation. Proc Natl Acad Sci USA 1999; 96: 13330–13335.
Smith JA. Neutrophils, host defense, and inflammation: A double-edged sword. J Leukoc Biol 1994; 56: 672–686.
Vachier I, Chanez P, Le Doucen C, Damon M, Descomps B, Godard P. Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients. Eur Respir J 1994; 7: 1585–1592.
Chanock SJ, el Benna J, Smith RM, Babior BM. The respiratory burst oxidase. J Biol Chem 1994; 269: 24519–24522.
Bass DA, ParceJW, Dechatelet LR, Szejda P, SeedsMC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J Immunol 1983; 130: 1910–1917.
Dusi S, Bianca VD, Donini M, Nadalini KA, Rossi F. Mechanisms of stimulation of the respiratory burst by TNF in nonadherent neutrophils. J Immunol 1996; 157: 4615–4623.
Coffer PJ, Burgering BMT, Peppelenbosch MP, Bos JL, Kruijer W. UV activation of receptor tyrosine kinase activity. Oncogene 1995; 11: 561–569.
Knebel A, Rahmsdorf HJ, Ullrich A, Herrlich P. Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents. EMBO J 1996; 15: 5314–5325.
Huang RP, Wu JX, Fan Y, Adamson ED. UV activates growth factor receptors via reactive oxygen intermediates. J Cell Biol 1996; 133: 211–220.
Schreck R, Riever P, Baeuerle PA. Reactive oxygen intermediates as apparently widely used messengers in activation of the NF-кB transcription factor and HIV-1. EMBO J 1991; 10: 2247–2258.
Pierce GB, Parchment RE, Lewellyn AL. Hydrogen peroxide as a mediator of programmed cell death in the blastocyst. Differentiation 1991; 46: 181–186.
Kasahara Y, Kazuyuki I, Yachie A, et al. Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils. Blood 1997; 89: 1748–1753.
Watson RW, Rotstein OD, Jimenez M, Parodo J, Marshall JC. Augmented intracellular glutathione inhibits Fas-triggered apoptosis of activated human neutrophils. Blood 1997; 89: 4175–4181.
Wedi B, Straede J, Wieland B, Kapp A. Eosinophil apoptosis is mediated by stimulators of cellular oxidative metabolisms and inhibited by antioxidants: Involvement of a thiol-sensitive redox regulation in eosinophil cell death. Blood 1999; 94: 2365–2373.
Yousefi S, Green DR, Blaser K, Simon HU. Protein-tyrosine phosphorylation regulates apoptosis in human eosinophils and neutrophils. Proc Natl Acad Sci USA 1994; 91: 10868–10872.
Ashkenazi A, Dixit VM. Death receptors: Signaling and modulation. Science 1998; 281: 1305–1308.
Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 1999; 17: 331–367.
Talley AK, Dewhurst S, Perry SW, et al. Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: Protection by the antioxidant N-acetylcysteine and the genes Bcl-2 and crmA. Mol Cell Biol 1995; 15: 2359–2366.
Cossarizza A, Franeschi C, Monti D, et al. Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: The role of mitochondria. Exp Cell Res 1995; 220: 232–240.
Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, JacobWA, FiersW. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitocohndrial functions. J Biol Chem 1992; 267: 5317–5323.
Schulze-Osthoff K, Beyaert R, Vandevoorde V, Haegeman G, FiersW. Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. EMBO J 1993; 12: 3095–3104.
Liu B, Andrieu Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem 1998; 273: 11313–11320.
Hebestreit H, Dibbert B, Balatti I, et al. Disruption of Fas receptor signaling by nitric oxide in eosinophils. J Exp Med 1998; 187: 415–425.
Wong GH, Goeddel DV. Induction of manganous superoxide dismutase by tumor necrosis factor: Possible protective mechanism. Science 1989; 242: 941–943.
Krammer PH. CD95 (APO-1/Fas)-mediated apoptosis: Live and let die. Adv Immunol 1999; 71: 163–210.
Um HD, Orenstein JM, Wahl SM. Fas mediates apoptosis in human monocytes by a reactive oxygen intermediate dependent pathway. J Immunol 1996; 156: 3469–3477.
Chiba T, Takahashi S, Sato N, Ishii S, Kikuchi K. Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells. Eur J Immunol 1996; 26: 1164–1169.
Delneste Y, Jeannin P, Sebille E, Aubry JP, Bonnefoy JY. Thiols prevent Fas (CD95)-mediated T cell apoptosis by downregulating membrane Fas expression. Eur J Immunol 1996; 26: 2981–2988.
Hug H, Strand S, Grambihler A, et al. Reactive oxygen intermdiates are involved in the induction of CD95 ligand mRNA expression by cytostatic drugs in hepatoma cells. J Biol Chem 1997; 272: 28191–28193.
Bauer MKA, Vogt M, Los M, Siegel J, Wesselborg S, Schulze-Osthoff K. Role of reactive oxygen intermediates in activation-induced CD95 (Apo/Fas) ligand expression. J Biol Chem 1998; 273: 8040–8055.
Simon HU, Yousefi S, Dibbert B, et al. Role for tyrosine phosphorylation and Lyn tyrosine kinase in Fas receptor-mediated apoptosis in eosinophils. Blood 1998; 92: 547–557.
Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309–1312.
Antonsson B, Conti F, Ciavatta A, et al. Inhibition of Bax channel-forming activity by Bcl-2. Science 1997; 277: 370–372.
Zamzami N, Marchetti P, Castedo M, et al. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 1995; 182: 367–377.
Muehl H, Sandau K, Bruene B, Briner VA, Pfeilschifter J. Nitric oxide donors induce apoptosis in glomerular mesangial cells, epithelial cells and endothelial cells. Eur J Pharmacol 1996; 317: 137–149.
Shami PJ, Sauls DL, Weinberg JB. Schedule and concentrationdependent induction of apoptosis in leukemia cells by nitric oxide. Leukemia 1998; 12: 1461–1466.
Hajri A, Metzger E, Vallat F, et al. Role of nitric oxide in pancreatic tumour growth-in vivo and in vitro studies. Br J Cancer 1998; 78: 841–849.
Cui S, Reichner JS, Matero RB, Albina JE. Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or-independent mechanism. Cancer Res 1994; 54: 2462–2467.
Filep JG, Baron C, Lachance S, Perreault C, Chan JSD. Involvement of nitric oxide in target-cell lysis andDNAfragmentation induced by murine natural killer cells. Blood 1996; 87: 5136–5143.
Fukuo K, Hata S, Suhara T, et al. Nitric oxide induces upregulation of Fas and apoptosis in vascular smooth muscle. Hypertension 1996; 27: 823–826.
Hortelano S, Dalloporta B, Zamzami N, et al. Nitric oxide induces apoptosis via triggering mitochondrial permeability transition. FEBS Letters 1997; 410: 373–377.
Messmer UK, Reed JC, Bruene B. Bcl-2 protects macrophages from nitric oxide-induced apoptosis. J Biol Chem 1996; 271: 20192–20197.
Shen YH, Wang XL, Wilcken DEL. Nitric oxide induces and inhibits apoptosis through different pathways. FEBS Letters 1998; 433: 125–131.
Ceneviva GD, Tzeng E, Hoyt DG, et al. Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery endothelial cells. Am J Physiol 1998; 19: L717-L728.
Sciorati C, Rovere P, Ferrarini M, Heltai S, Manfredi AA, Clementi E. Autocrine nitric oxide modulates CD95-induced apoptosis in γ/δ T lymphocytes. J Biol Chem 1997; 272: 23211–23215.
Kim YM, De Vera ME, Wathins SC, Billar SC. Nitric oxide protects cultured rat hepatocytes from tumor necrosis factoralpha-induced apoptosis by inducing heat shock protein 70 expression. J Biol Chem 1997; 272: 1402–1411.
Arrigo AP. Small stress proteins: Chaperones that act as regulators of intracellular redox state and programmed cell death. Biol Chem 1998; 379: 19–26.
Dimmeler S, Haendeler J, Nehls M, Zeiher AM. Suppression of apoptosis by nitric oxide via inhibition of interleukin-1-beta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J Exp Med 1997; 185: 601–607.
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Simon, HU., Haj-Yehia, A. & Levi-Schaffer, F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5, 415–418 (2000). https://doi.org/10.1023/A:1009616228304
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DOI: https://doi.org/10.1023/A:1009616228304