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Tumor necrosis factor-α plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide

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Abstract

Treatment with the nitric oxide-(NO)-generating compoundS-nitroso-N-acetylpenicillamine protected cultured L929 cells from apoptosis induced by tumor necrosis factor-α (TNF-α) plus actinomycin D, as determined by the detection of DNA fragmentation and morphological changes. NO also prevented an enhancement of the production of reactive oxygen intermediates by TNF-α plus actinomycin D, as assessed by the oxidation of dihydrorhodamine 123 and hydroethidine. Because the inhibition of mitochondrial respiration by rotenone or antimycin A suppressed the increased oxidation of both dihydrorhodamine 123 and hydroethidine, it was suggested that TNF-α accelerated the leakage of reactive oxygen intermediates from the mitochondrial electron transport system. Polarography showed that NO reversibly inhibited mitochondrial respiration at either complexes I–III, II–III, or IV, thus suggesting the inhibition of cytochrome oxidase. Taken together, these findings indicate that the decreased mitochondrial formation of reactive oxygen intermediates in the presence of NO might have a protective effect against TNF-α plus actinomycin D-induced apoptosis.

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References

  1. Doughty LA, Kaplan SS, Carcillo JA (1996) Inflammatory cytokine and nitric oxide responses in pediatric sepsis and organ failure. Crit Care Med 24:1137–1143

    Article  PubMed  CAS  Google Scholar 

  2. Wong GHW, Goeddel DV (1988) Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science 242:941–944

    Article  PubMed  CAS  Google Scholar 

  3. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W (1992) Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. J Biol Chem 267:5317–5323

    PubMed  CAS  Google Scholar 

  4. Shoji Y, Uedono Y, Ishikura H, Takeyama N, Tanaka T (1995) DNA damage induced by tumor necrosis factor-α in L929 cells is mediated by mitochondrial oxygen radical formation. Immunology 84:543–548

    PubMed  CAS  Google Scholar 

  5. Hennet T, Richter C, Peterhans E (1993) Tumor necrosis factor-α induces superoxide anion generation in mitochondria of L929 cells. Biochem J 289:587–592

    PubMed  CAS  Google Scholar 

  6. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    Article  PubMed  CAS  Google Scholar 

  7. Ma TT, Ischiropoulos H, Brass CA (1995) Endotoxin-stimulated nitric oxide production increases injury and reduces rat liver chemiluminescence during reperfusion. Gastroenterology 108: 463–469

    Article  PubMed  CAS  Google Scholar 

  8. Wink DA, Hanbauer I, Krishna MC, Degraff W, Gamson J, Mitchell JB (1993) Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species. Proc Natl Acad Sci USA 90:9813–9817

    Article  PubMed  CAS  Google Scholar 

  9. Kim Y-M, de Vera ME, Watkins SC, Billiar TR (1997) Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-α-induced apoptosis by inducing heat shock protein 70 expression. J Biol Chem 272:1402–1411

    Article  PubMed  CAS  Google Scholar 

  10. Fehsel K, Kröncke K-D, Meyer KL, Huber H, Wahn V, Kolb-Bachofen V (1995) Nitric oxide induces apoptosis in mouse thymocytes. J Immunol 155:2858–2865

    PubMed  CAS  Google Scholar 

  11. Yasmin W, Strynadka KD, Schulz R (1997) Generation of peroxynitrite contributes to ischemia-reperfusion injury in isolated rat hearts. Cardiovasc Res 33:422–432

    Article  PubMed  CAS  Google Scholar 

  12. Pastorino JG, Simbula G, Yamamoto K, Glascott PA Jr, Rothman RJ, Farber JL (1996) The cytotoxicity of tumor necrosis factor depends on induction of the mitochondrial permeability transition. J Biol Chem 271:29792–29798

    Article  PubMed  CAS  Google Scholar 

  13. Ruff MR, Gifford GE (1981) Rabbit tumor necrosis factor: mechanism of action. Infect Immun 31:380–385

    PubMed  CAS  Google Scholar 

  14. Jones KH, Senft JA (1985) An improved method to determine cell viability by simultaneous staining with fluorescein diacetatepropidium iodide. J Histochem Cytochem 33:77–79

    Article  PubMed  CAS  Google Scholar 

  15. Duke RC, Cohen JJ (1986) IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res 5:289–299

    PubMed  CAS  Google Scholar 

  16. Royall JA, Ischiropoulos H (1993) Evaluation of 2′,7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. tArch Biochem Biophys 302:348–355

    Article  CAS  Google Scholar 

  17. Castedo M, Macho A, Zamzami N, Hirsch T, Marchetti P, Uriel J, Kroemer G (1995) Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo. Eur J Immunol 25:3277–3284

    Article  PubMed  CAS  Google Scholar 

  18. Zamai L, Falcieri E, Zauli G, Cataldi A, Vitale M (1993) Optimal detection of apoptosis by flow cytometry depends on cell morphology. Cytometry 14:891–897

    Article  PubMed  CAS  Google Scholar 

  19. Iida R, Takeyama N, Iida N, Tanaka T (1991) Characterization of overt carnitine palmitoyltransferase in rat platelets: involvement of insulin on its regulation. Mol Cell Biochem 103:23–30

    Article  PubMed  CAS  Google Scholar 

  20. Chun S-Y, Eisenhauer KM, Kubo M, Hsueh AJW (1995) Interleukin-1⨿ suppresses apotposis in rat ovarian follicles by increasing nitric oxide production. Endocrinology 136:3120–3127

    Article  PubMed  CAS  Google Scholar 

  21. Genaro AM, Hortelano S, Alvarez A, Martínez-A C, Boscá L (1995) Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels. J Clin Invest 95:1884–1890

    Article  PubMed  CAS  Google Scholar 

  22. Mannick JB, Asano K, Izumi K, Kieff E, Stamler JS (1994) Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell 79:1137–1146

    Article  PubMed  CAS  Google Scholar 

  23. Beauvais F, Michel L, Dubertret L (1995) The nitric oxide donors, azide and hydroxylamine, inhibit the programmed cell death of cytokine-deprived human eosinophils. FEBS Lett 361:229–232

    Article  PubMed  CAS  Google Scholar 

  24. Packer MA, Murphy MP (1995) Peroxynitrite formed by simultaneous nitric oxide and superoxide generation causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation. Eur J Biochem 234:231–239

    Article  PubMed  CAS  Google Scholar 

  25. Brown GC, Bolaños JP, Heales SJR, Clark J (1995) Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neurosci Lett 193:201–204

    Article  PubMed  CAS  Google Scholar 

  26. Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298

    Article  PubMed  CAS  Google Scholar 

  27. Bolaõs JP, Peuchen S, Heales SJR, Land JM, Clark JB (1994) Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes. J Neurochem 63:910–916

    Article  Google Scholar 

  28. Radi R, Rodriguez M, Castro L, Telleri R (1994) Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys 308:89–95

    Article  PubMed  CAS  Google Scholar 

  29. Xie Y-W, Wolin MS (1996) Role of nitric oxide and its interaction with superoxide in the suppression of cardiace muscle mitochondrial respiration: involvement in response to hypoxia/reoxygenation. Circulation 94:2580–2586

    PubMed  CAS  Google Scholar 

  30. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA (1994) Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation: formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 269:26066–26075

    PubMed  CAS  Google Scholar 

  31. Bohlinger I, Leist M, Barsig J, Uhlig S, Tiegs G, Wendel A (1995) Interleukin-1 and nitric oxide protect against tumor necrosis factor α-induced liver injury through distinct pathways. Hepatology 22:1829–1837

    PubMed  CAS  Google Scholar 

  32. Kaneto H, Fujii J, Seo HG, Suzuki K, Matsuoka T, Nakamura M, Tastumi H, Yamasaki Y, Kamada T, Taniguchi N (1995) Apoptotic cell death triggered by nitric oxide in pancreatic β-cells. Diabetes 44:733–738

    Article  PubMed  CAS  Google Scholar 

  33. Laskin DL, del Valle MR, Heck DE, Hwang S-M, Ohnishi ST, Durham SK, Goller NL, Laskin JD (1995) Hepatic nitric oxide production following acute endotoxemia in rats is mediated by increased inducible nitric oxide synthase gene expression. Hepatology 22:223–234

    PubMed  CAS  Google Scholar 

  34. Beßmer UK, Lapetina EG, Brüne B (1995) Nitric oxide-induced apoptosis in RAW 264.7 macrophages is antagonized by protein kinase C- and protein kinase A-activating compounds. Mol Pharmacol 47:757–765

    Google Scholar 

  35. Lipton SA, Choi Y-B, Pan Z-H, Lei SZ, Chen H-SV, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632

    Article  PubMed  CAS  Google Scholar 

  36. Lysiak JJ, Hussaini IM, Webb DJ, Glass WF II, Allietta M, Gonias SL (1995) α-Macroglobulin functions as a cytokine carrier to induce nitric oxide synthesis and cause nitric oxidedependent cytotoxicity in the RAW 264.7 macrophage cell line. J Biol Chem 270:21919–21927

    Article  PubMed  CAS  Google Scholar 

  37. Meßmer UK, Brüne B (1996) Nitric oxide (NO) in apoptotic versus necrotic RAW 264.7 macrophage cell death: the role of NO-donor exposure, NAD1 content, and p53 accumulation. Arch Biochem Biophys 327:1–10

    Article  PubMed  Google Scholar 

  38. Dawson VL, Kizushi VM, Huang PL, Snyder SH, Dawson TM (1996) Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice. J Neurosci 16:2479–2487

    PubMed  CAS  Google Scholar 

  39. Billiar TR, Curran RD, Harbrecht BG, Stuehr DJ, Demetris AJ, Simmons RL (1990) Modulation of nitrogen oxide synthesis in vivo:N G-monomethyl-l-arginine inhibit endotoxin-induced nitrite/nitrate biosynthesis whie promoting hepatic damage. J Leuk Biol 48:565–569

    CAS  Google Scholar 

  40. Schmidt HHHW, Walter U (1994) NO at work. Cell 78: 919–925

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency and Critical Care Medicine, Kansai Medical University, 10-15 Fumizono-cho, 570-8507, Moriguchi, Osaka, Japan

    Shigeru Hakoda, Hiroyasu Ishikura, Naoshi Takeyama & Takaya Tanaka

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  1. Shigeru Hakoda
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  2. Hiroyasu Ishikura
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  3. Naoshi Takeyama
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  4. Takaya Tanaka
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Hakoda, S., Ishikura, H., Takeyama, N. et al. Tumor necrosis factor-α plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide. Surg Today 29, 1059–1067 (1999). https://doi.org/10.1007/s005950050645

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  • DOI: https://doi.org/10.1007/s005950050645

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