Abstract
Oncogenic transformed fibroblasts are characterized by extracellular superoxide anion generation through a membrane-associated NADPH oxidase. After cellular glutathione depletion, extracellular reactive oxygen species (ROS) generated by transformed fibroblasts exhibit a strong apoptosis-inducing potential. As apoptosis induction under glutathione depletion is inhibited by catalase, the NADPH oxidase inhibitor apocynin, superoxide dismutase, the hydroxyl radical scavenger terephthalate and the iron chelator deferoxamine, the metal-catalysed Haber-Weiss reaction seems to be the responsible signaling mechanism. In contrast to extracellular ROS, intracellular ROS play no role for apoptosis induction in glutathione-depleted transformed fibroblasts initially, since a high level of intracellular catalase scavenges intracellular hydrogen peroxide. Intracellular catalase seems to be induced by extracellular hydrogen peroxide, as pretreatment of transformed fibroblasts with exogenous catalase downmodulates endogenous catalase and renders glutathione-depleted transformed cells susceptible for the effect of endogenous hydrogen peroxide. In contrast to transformed fibroblasts, nontransformed glutathione-depleted fibroblasts do not generate substantial extracellular ROS, but apoptosis is efficiently induced in these cells by intracellular ROS. Our data show that extracellular ROS of transformed fibroblasts exhibit redox-related signaling and at the same time represent a potential apoptosis-inducing hazard through the metal-catalysed Haber-Weiss reaction.
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References
Antunes F, Cadenas E . 2000 FEBS Lett. 475: 121–126
Aoshima H, Satoh T, Sakai N, Yamada M, Enokido Y, Ikeuchi T, Hatanaka H . 1997 Biochem. Biophys. Acta 1345: 35–42
Aruoma OI, Halliwell B, Hoey BM, Butler J . 1988 Biochem. J. 256: 251–256
Barnes A, Bowden TJ, Horne MT, Ellis AE . 1999 Microb. Pathogenesis 26: 149–158
Bauer G, Dormann S, Engelmann I, Schulz A, Saran M . 2000 In Handbook of Exp. Pharmacology Vol. 142: Cameron RG and Feuer G (eds) Berlin, Heidelberg, New York: Springer Verlag pp 275–318
Bauer G . 2000 Anticancer Res. 20: 4115–4140
Beck E, Schäfer R, Bauer G . 1997 Exp. Cell. Res. 234: 47–56
Bielski BHJ, Allen AO . 1977 J. Phys. Chem. 81: 1048–1050
Bittinger F, Gonzalez-Garcia JL, Klein CL, Brochhausen C, Offner F, Kirkpatrick CJ . 1998 Melanoma Res. 8: 381–387
Boveris A, Chance B . 1973 Biochem. J. 134: 707–716
Cadenas E, Davies KJA . 2000 Free Rad. Biol. Med. 29: 222–230
Candeias LP, Patel KB, Stratford ML, Wardmann P . 1993 FEBS Lett. 333: 151–153
Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee R K . 1997 Free Rad. Biol. Med. 23: 8–18
Deichman GI, Kashkina LM, Mizenina OA, Gorojanskaya EG, Nikiforov MA, Gudkov AV, Dyakova NA, Komelkov AV, Prilutskaya MO, Kushlinsky NE, Tatosyan AG . 1996 Int. J. Cancer 66: 747–752
Deichman GI, Matveeva VA, Kashkina LM, Dyakova NA, Uvarova EN, Nikiforov MA, Gudkov AV . 1998 Int. J. Cancer 75: 277–283
Engelmann I, Dormann S, Saran M, Bauer G . 2000 Redox Rep. 5: 207–214
Enoiu M, Aberkane H, Salazar JF, Leroy P, Groffen J, Siest G, Wellman M . 2000 Free Rad. Biol. Med. 29: 825–833
Faure H, Coudray C, Mousseau M, Ducros V, Douki T, Bianchini F, Cadet J, Favier A . 1996 Free Rad. Biol. Med. 20: 979–983
Fridovich I . 1995 Annu. Rev. Biochem. 64: 97–112
Girotti AW . 1998 J. Lipid Res. 39: 1529–1542
Gorczyca W, Gong J, Darzynkiewicz Z . 1993 Cancer Res. 53: 1945–1951
Häufel T, Bauer G . 2001 Anticancer Res. 21: 2617–2628
Heigold S, Bauer G . 2002 J. Leukocyte Biology 23: 939–941
Heigold S, Sers C, Bechtel W, Ivanovas B, Schäfer R, Bauer G . 2002 Carcinogenesis in press
Held KD, Sylvester FC, Hopcia KL, Biaglow JE . 1996 Radiat. Res. 145: 542–553
Herdener M, Heigold S, Saran M, Bauer G . 2000 Free Rad. Biol. Med. 29: 1260–1271
Hipp ML, Bauer G . 1997 Oncogene 15: 791–797
Hirsch T, Marzo I, Kroemer G . 1997 Bioscience Rep. 17: 67–76
Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon E R, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ . 1997 Science 275: 1649–1652
Johnson D, Agochiya M, Samejima K, Earnshaw W, Frame M, Wyke J . 2000 Cell Death Differ. 7: 685–696
Jürgensmeier JM, Panse J, Schäfer R, Bauer G . 1997 Int. J. Cancer 70: 587–589
Jürgensmeier JM, Schmitt CP, Viesel E, Höfler P, Bauer G . 1994 Cancer Res. 54: 393–398
Kehrer JP . 2000 Toxicol. 149: 43–50
Kettle AJ, Gedye CA, Winterbourn CC . 1997 Biochem. J. 321: 503–508
Koppenol WH . 2001 Redox Rep. 6: 229–234
Kroemer G, Zamzami N, Susin SA . 1997 Immunol. Today 18: 44–51
Lai CC, Peng M, Huang L, Huang WH, Chiu TH . 1996 J. Mol. Cell. Cardiol. 28: 1157–1163
Li PF, Dietz R, Von Harsdorf R . 1997a Circulation 96: 3602–3609
Li PF, Dietz R, Von Harsdorf R . 1997b FEBS Lett. 404: 249–252
Morre DJ, Reust T . 1997 J. Bioenerg. Biomembr. 29: 281–289
Morre DJ, Chueh PJ, Morre DM . 1995 Proc. Natl. Acad. Sci. USA 92: 1831–1835
Mylonas C, Kouretas D . 1999 in vivo 13: 295–310
Nappi AJ, Vass E . 1998 Biochem. Biophys. Acta 1380: 55–63
Oettl K, Wirleitner B, Baier-Bitterlich G, Grammer T, Fuchs D, Reibnegger G . 1999 Biochem. Biophys. Res. Co. 264: 262–267
Oyama Y, Noguchi S, Nakata M, Okada Y, Yamazaki Y, Funai M, Chikahisa L, Kanemaru K . 1999 Eur. J. Pharmacol. 384: 47–52
Paul K, Bauer G . 2001 Anticancer Res. 21: 3237–3246
Rauen U, De Groot H . 1998 Free Rad. Biol. Med. 24: 1316–1323
Roehrdanz E, Kahl R . 1998 Free Rad. Biol. Med. 24: 27–38
Rollet-Labelle E, Grange M-J, Elbim C, Marquetty C, Gougerot-Pocidalo M-A, Pasquier C . 1998 Free Rad. Biol. Med. 24: 563–572
Rosen H, Klebanoff SJ . 1979 J. Clin. Invest. 64: 1725–1729
Saran M, Bors W . 1994 Chemico-biol. Interact. 90: 35–45
Saran M, Summer KH . 1999 Free Radical Res. 31: 429–436
Schimmel M, Bauer G . 2001 Int. J. Oncol. 19: 299–304
Schwieger A, Bauer L, Hanusch J, Sers C, Schäfer R, Bauer G . 2001 Carcinogenesis 22: 1385–1392
Shi X, Dalal NS . 1992 Arch. Biochem. Biophys. 292: 323–327
Suh Y-A, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD . 1999 Nature 401: 79–82
T'Hart BA, Simons JM, Knaan Shanzer S, Bakker NPM, Labadie RP . 1990 Free Rad. Biol. Med. 9: 127–132
Stolk J, Hiltermann TJN, Dijkman JH, Verhoeven AJ . 1994 Am. J. Resp. Cell Mol. 11: 95–102
Van den Dobbelsteen DJ, Nobel CSJ, Schlegel J, Cotgreave IA, Orrenius S, Slater AFG . 1996 J. Biol. Chem. 271: 15420–15427
Xu Y, Nguyen Q, Lo DC, Czaja MJ . 1997 J. Cell. Physiol. 170: 192–199
Zucker B, Hanusch J, Bauer G . 1997 Cell Death Differ. 4: 388–395
Acknowledgements
This work was supported by the Dr Mildred-Scheel-Stiftung für Krebsforschung (grant 10-1177-Ba3).
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Schimmel, M., Bauer, G. Proapoptotic and redox state-related signaling of reactive oxygen species generated by transformed fibroblasts. Oncogene 21, 5886–5896 (2002). https://doi.org/10.1038/sj.onc.1205740
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DOI: https://doi.org/10.1038/sj.onc.1205740
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