Changes in GSH-antioxidant system induced by daunorubicin in human normal and diabetic fibroblasts.
Languages of publication
We investigated the effect of daunorubicin on glutathione content and activity of GSH-related enzymes in cultured normal and diabetic human fibroblasts. Cells were incubated with 4 μM daunorubicin (DNR) for 2 h followed by culture in drug-free medium for up to 72 h. Treatment of diabetic cells with the drug caused a time-dependent depletion of intracellular GSH and a decrease of the GSH to total glutathione ratio. GSH depletion was accompanied by apoptotic changes in morphology of the nucleus. Analysis of GSH-related enzymes showed a significant increase of the activities of Se-dependent and Se-independent peroxidases and glutathione S-transferase. In contrast, glutathione reductase activity was reduced by 50%. Significant differences between normal and diabetic cells exposed to DNR were observed in the level of GST and Se-dependent glutathione peroxidase activities. These findings indicated that daunorubicin efficiently affects the GSH antioxidant defense system both in normal and diabetic fibroblasts leading to disturbances in glutathione content as well as in the activity of GSH-related enzymes.
- Ahlemeyer B, Krieglstein J. (2000) Inhibition of glutathione depletion by retinoic acid and tocopherol protects cultured neurons from staurosporine-induced oxidative stress and apoptosis. Neurochem Int.; 36: 1-5.
- Akerboom TP, Sies H. (1981) Assay of glutathione, glutathione disulfide and glutathione mixed disulfides in biological samples. Meth Enzymol.; 77: 373-82.
- Armstrong JS, Steinauer KK, Hornung B, Irish JM, Lecane P, Birrell GW, Peehl DM, Knox SJ. (2002) Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ.; 9: 252-63.
- Baez S, Segura-Aguilar J, Widersten M, Johnson AS, Mannervik B. (1997) Glutathione transferases catalyse the detoxification of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J.; 324: 25-8.
- Bladeren van PJ. (2000) Glutathione conjugation as a bioactivation reaction. Chem Biol Interact.; 129: 61-76.
- Carlberg J, Mannervik B. (1975) Purification and characterization of flavoenzyme glutathione reductase from rat liver. J Biol Chem.; 250: 5475-80.
- Chiba T, Takahashi S, Sato N, Ishii S, Kikuchi K. (1996) Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells. Eur J Immunol.; 26: 1164-9.
- Cnubben NH, Rietjens JM, Wortelboer H, van Zanden J, van Bladeren PJ. (2001) The interplay of glutathione-related processes in antioxidant defense. Environ Toxicol Pharmacol.; 10: 141-52.
- Di Simplicio P, de Giorgio LA, Cardaioli E, Lecis R, Miceli M, Rossi R, Anichini R, Mian M, Seghieri G, Franconi F. (1995) Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin-dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications. Eur J Clin Invest.; 25: 665-9.
- Gewirtz DA. (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol.; 57: 727-41.
- Griffith OW. (1999) Biological and pharmacological regulation of mammalian glutathione synthesis. Free Radic Biol Med.; 27: 922-35.
- Hammond CL, Lee TK, Ballatori N. (2001) Novel roles for glutathione in gene expression, cell death, and membrane transport of organic solutes. J Hepatol.; 34: 946-54.
- Hayes JD, McLellan JJ. (1999) Glutathione and glutathione-dependent enzymes represent a coordinately regulated defence against oxidative stress. Free Radic Res.; 31: 273-300.
- Julicher RH, van der Laarse A, Stevrenberg L, Bloys van Treslong CH, Bast A, Noordhoek J. (1985) The involvement of an oxidative mechanism in the adriamycin-induced toxicity in neonatal rat heart cell cultures. Res Commun Chem Pathol Pharmacol.; 47: 35-47.
- Lowry OH, Rosebrough NJ, Farr AL, Randal RJ. (1951) Protein measurement with the Folin phenol reagent. J Biol Chem.; 193: 265-75.
- Meister A. (1995) Glutathione metabolism. Meth Enzymol.; 251: 3-7.
- Mukherjee B, Anbazhagan S, Roy A, Ghosh R, Chatterjee M. (1998) Novel implications of the potential role of selenium on antioxidant status in streptozotocin-induced diabetic mice. Biomed Pharmacother.; 52: 89-95.
- Meyers C, Mimnaugh EC, Jeh GC, Sinha BK. (1988) Biochemical mechanisms of tumor cell kill by anthracyclines. In: Anthracycline and anthracenedione-based anticancer drugs. Lown W. ed, pp 527-69. Elsevier, Amsterdam.
- O'Brien PJ. (1991) Molecular mechanisms of quinone cytotoxicity. Chem-Biol Interact.; 80: 1-41.
- Olson RD, MacDonald JS, van Boxtel CJ, Boerth RC, Harbison RD, Slonim AE, Freeman RW, Oates JA. (1980) Regulatory role of GSH and soluble sulfhydryl groups in the toxicity of adriamycin. J Pharmacol Exp Ther.; 215: 450-4.
- Palmer HJ, Paulson KE. (1997) Reactive oxygen species and antioxidants in signal transduction and gene expression. Nutr Rev.; 55: 353-61.
- Paranka NS, Dorr RT. (1994) Effect of doxorubicin on glutathione and glutathione-dependent enzymes in cultured rat heart cells. Anticancer Res.; 14: 2047-52.
- Powis G. (1989) Free radical formation by antitumor quinones. Free Radic Biol Med.; 6: 63-101.
- Przybylska M, Koceva-Chyła A, Rózga B, Jóźwiak Z. (2001) Cytotoxicity of daunorubicin in trisomic (+21) human fibroblasts: relation to drug uptake and cell membrane fluidity. Cell Biol Int.; 25: 157-70.
- Ratan RR, Murphy TM, Baraban JM. (1994) Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem.; 62: 376-9.
- Rice-Evans CA, Diplock AT, Symons MC. (1991) Techniques in free radical research. Elsevier, Amsterdam.
- Samiec PS, Drews-Botsch C, Flagg EW, Kurtz JC, Sternberg P Jr, Reed RL, Jones DP. (1998) Glutathione in human plasma. Decline in association with aging age-related macular degeneration and diabetes. Free Radic Biol Med.; 24: 699-704.
- Shimizu E, Hashimoto K, Komatsu N, Jyo M. (2002) Roles of endogenous glutathione levels on 6-hydroxydopamine-induced apoptotic neuronal cell death in human neuroblastoma SK-N-SH cells. Neuropharmacology; 43: 434-43.
- Sies H. (1999) Glutathione and its role in cellular functions. Free Radic Biol Med.; 27: 916-21.
- Srivastava SK, Ansari NH, Liu S, Izban A, Das B, Szabo G, Bhatnagar A. (1989) The effect of oxidants on biomembranes and cellular metabolism. Mol Cell Biochem.; 91: 149-57.
- Tan S, Sagara Y, Liu Y, Maher D, Schubert D. (1998) The regulation of reactive oxygen species production during programmed cell death. J Cell Biol.; 141: 1423-32.
- Tew KD. (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res.; 54: 4313-20.
- Tew KD, Ronai Z. (1999) GST function in drug and stress response. Drug Resist Updat.; 2: 143-7.
- Thornalley PJ, McLellan AC, Lo TW, Benn J, Sonksen PH. (1996) Negative association between erythrocytes reduced glutathione concentration and diabetic complications. Clin Sci.; 91: 575-82.
- Wernerman J, Luo J-L, Hammarqvist F. (1999) Glutathione status in critically-ill patients: possibility of modulation by antioxidants. Proc Nutr Soc.; 58: 677-80.
- Zatorska A, Jóźwiak Z. (2002) Involvement of glutathione and glutathione-related enzymes in the protection of normal and trisomic human fibroblasts against daunorubicin. Cell Biol Int.; 26: 383-91.
- Zucker B, Hanusch J, Bauer G. (1997) Glutathione depletion in fibroblasts is the basis for apoptosis-induction by endogenous reactive oxygen species. Cell Death Differ.; 4: 388-95.
Publication order reference