Role of reactive oxygen species (ROS) in apoptosis induction

Apoptosis volume 5, pages415–418(2000)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

References

  1. 1.

    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.

    Google Scholar 

  2. 2.

    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.

    Google Scholar 

  3. 3.

    Smith JA. Neutrophils, host defense, and inflammation: A double-edged sword. J Leukoc Biol 1994; 56: 672–686.

    Google Scholar 

  4. 4.

    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.

    Google Scholar 

  5. 5.

    Chanock SJ, el Benna J, Smith RM, Babior BM. The respiratory burst oxidase. J Biol Chem 1994; 269: 24519–24522.

    Google Scholar 

  6. 6.

    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.

    Google Scholar 

  7. 7.

    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.

    Google Scholar 

  8. 8.

    Coffer PJ, Burgering BMT, Peppelenbosch MP, Bos JL, Kruijer W. UV activation of receptor tyrosine kinase activity. Oncogene 1995; 11: 561–569.

    Google Scholar 

  9. 9.

    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.

    Google Scholar 

  10. 10.

    Huang RP, Wu JX, Fan Y, Adamson ED. UV activates growth factor receptors via reactive oxygen intermediates. J Cell Biol 1996; 133: 211–220.

    Google Scholar 

  11. 11.

    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.

    Google Scholar 

  12. 12.

    Pierce GB, Parchment RE, Lewellyn AL. Hydrogen peroxide as a mediator of programmed cell death in the blastocyst. Differentiation 1991; 46: 181–186.

    Google Scholar 

  13. 13.

    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.

    Google Scholar 

  14. 14.

    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.

    Google Scholar 

  15. 15.

    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.

    Google Scholar 

  16. 16.

    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.

    Google Scholar 

  17. 17.

    Ashkenazi A, Dixit VM. Death receptors: Signaling and modulation. Science 1998; 281: 1305–1308.

    Google Scholar 

  18. 18.

    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.

    Google Scholar 

  19. 19.

    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.

    Google Scholar 

  20. 20.

    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.

    Google Scholar 

  21. 21.

    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.

    Google Scholar 

  22. 22.

    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.

    Google Scholar 

  23. 23.

    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.

    Google Scholar 

  24. 24.

    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.

    Google Scholar 

  25. 25.

    Wong GH, Goeddel DV. Induction of manganous superoxide dismutase by tumor necrosis factor: Possible protective mechanism. Science 1989; 242: 941–943.

    Google Scholar 

  26. 26.

    Krammer PH. CD95 (APO-1/Fas)-mediated apoptosis: Live and let die. Adv Immunol 1999; 71: 163–210.

    Google Scholar 

  27. 27.

    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.

    Google Scholar 

  28. 28.

    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.

    Google Scholar 

  29. 29.

    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.

    Google Scholar 

  30. 30.

    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.

    Google Scholar 

  31. 31.

    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.

    Google Scholar 

  32. 32.

    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.

    Google Scholar 

  33. 33.

    Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309–1312.

    Google Scholar 

  34. 34.

    Antonsson B, Conti F, Ciavatta A, et al. Inhibition of Bax channel-forming activity by Bcl-2. Science 1997; 277: 370–372.

    Google Scholar 

  35. 35.

    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.

    Google Scholar 

  36. 36.

    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.

    Google Scholar 

  37. 37.

    Shami PJ, Sauls DL, Weinberg JB. Schedule and concentrationdependent induction of apoptosis in leukemia cells by nitric oxide. Leukemia 1998; 12: 1461–1466.

    Google Scholar 

  38. 38.

    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.

    Google Scholar 

  39. 39.

    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.

    Google Scholar 

  40. 40.

    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.

    Google Scholar 

  41. 41.

    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.

    Google Scholar 

  42. 42.

    Hortelano S, Dalloporta B, Zamzami N, et al. Nitric oxide induces apoptosis via triggering mitochondrial permeability transition. FEBS Letters 1997; 410: 373–377.

    Google Scholar 

  43. 43.

    Messmer UK, Reed JC, Bruene B. Bcl-2 protects macrophages from nitric oxide-induced apoptosis. J Biol Chem 1996; 271: 20192–20197.

    Google Scholar 

  44. 44.

    Shen YH, Wang XL, Wilcken DEL. Nitric oxide induces and inhibits apoptosis through different pathways. FEBS Letters 1998; 433: 125–131.

    Google Scholar 

  45. 45.

    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.

    Google Scholar 

  46. 46.

    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.

    Google Scholar 

  47. 47.

    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.

    Google Scholar 

  48. 48.

    Arrigo AP. Small stress proteins: Chaperones that act as regulators of intracellular redox state and programmed cell death. Biol Chem 1998; 379: 19–26.

    Google Scholar 

  49. 49.

    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.

    Google Scholar 

Download references

Author information

Affiliations

  1. Department of Pharmacology, University of Bern, Bern, Switzerland

    H.-U. Simon

  2. Department of Pharmaceutics, School of Pharmacy, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

    A. Haj-Yehia & F. Levi-Schaffer

Authors
  1. H.-U. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Haj-Yehia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Levi-Schaffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • apoptosis
  • death receptors
  • inflammation
  • reactive oxygen species (ROS)