Effects of glutathione on mitochondrial DNA and antioxidant enzyme activities in Drosophila melanogaster

Yıl 2022, Cilt: 9 Sayı: 4, 377 - 386, 21.12.2022

Hülya Yıldız

https://doi.org/10.21448/ijsm.1084592

Öz

The free radical theory in aging assumes that the accumulation of macromolecular damage induced by toxic reactive oxygen species plays a central role in the aging process. The intake of nutritional antioxidants can prevent this damage by neutralizing reactive oxygen derivatives. Glutathione (GSH; en-L-Glutamyl-L-cysteinyl glycine) is the lowest molecular weight thiol in the cells and as a cofactor of many enzymes and a potent antioxidant plays an important role in maintaining normal cell functions by destroying toxic oxygen radicals. In this study, the effects of GSH on SOD, GST and catalase enzymes and mtDNA damage were investigated at various time intervals by giving reduced glutathione to Drosophila. It was observed that 3-week GSH administration did not have a statistically significant effect on SOD and GST activities whereas GSH application decreased the catalase enzyme activities significantly. Although the decrease in antioxidant capacity with age was observed in SOD and catalase enzymes, such a situation was not observed in GST enzyme activities. There was no statistically significant difference between the control and GSH groups in mtDNA copy number values, while in the GSH group, oxidative mtDNA damage was high. These results may be due to the prooxidant effect of GSH at the dose used in this study.

Anahtar Kelimeler

Glutathione, Catalase, GST, SOD, mtDNA

Destekleyen Kurum

TÜBİTAK

Proje Numarası

2209 A

Kaynakça

• Abreu, I.A., & Cabelli, D.E. (2010). Superoxide dismutases-a review of the metal-associated mechanistic variations. Biochimica Biophysica Acta, 1804(2), 263 274. https://doi.org/10.1016/j.bbapap.2009.11.005
• Aebi, S., Assereto, R., & Lauterburg, B.H. (1991). High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. European Journal of Clinical Investigation, 21(1), 103-110. https://doi.org/10.1111/j.1365-2362.1991.tb01366.x
• Allen, J., & Bradley, R.D. (2011). Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. The Journal of Alternative and Complementary Medicine, 17(9), 827–833. https://doi.org/10.1089/acm.2010.0716
• Ames, B.N., Shigenaga, M.K., & Hagen, T.M. (1993). Oxidants, antioxidants and the degenerative diseases of aging. Proceedings of the National Academy of Sciences, 90(1), 7915 7922. https://doi.org/10.1073/pnas.90.17.7915
• Arjinpathana, N., & Asawanonda, P. (2012). Glutathione as an oral whitening agent: A randomized, double-blind, placebo-controlled study. Journal of Dermatological Treatment, 23, 97–102. https://doi.org/10.3109/09546631003801619
• Armstrong, J.S., & Jones, D.P. (2002). Glutathione depletion enforces the mitochondrial permeability transition and causes cell death in Bcl-2 overexpressing HL60 cells. Federation of American Socities for Experimental Biology, 16, 1263 1265. https://doi.org/10.1096/fj.02-0097fje
• Ayer, A., Tan, S.X., Grant, C.M., Meyer, A.J., Dawes, I.W. & Perrone, G.G. (2010). The critical role of glutathione in maintenance of the mitochondrial genome. Free Radical Biology & Medicine, 49(12), 1956 1968. https://doi.org/10.1016/J.Freeradbiomed.2010.09.023
• Aw, T.Y., Wıerbızcka, G., & Jones, D.P. (1991). Oral Glutathione increases tissue glutathione in vivo. Chemico-Biological Interactions, 80, 89-97. https://doi.org/10.1016/0009-2797(91)90033-4
• Bajic, V.P. Van Neste, C., Obradovic, M., Zafirovic, S., Radak, D., Bajic, V.B., Essack, M., & Isenovic, E.R. (2019). Glutathione "Redox Homeostasis" and Its Relation to Cardiovascular Disease. Oxidative Medicine Cellular Longevity, Article ID 5028181. 14p. https://doi.org/10.1155/2019/5028181
• Benard, O., & Balasubramanian, K.A. (1993). Effect of oxidant exposure on thiol status in the intestinal mucosa. Biochemical Pharmacology, 45, 2011- 2015.https://doi.org/10.1016/0006-2952(93)90011-K
• Choi, I.Y., Lee, P., & Hughes, A.J. (2016). Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis. Multiple Sclerosis Journal, 23(1), 956 962. https://doi.org/10.1177/1352458516669441
• Circu, M.L., & Aw T.Y. (2012). Glutathione and modulation of cell apoptosis. Biochimica et Biophysica Acta, 1823, 1767–1777. https://doi.org/10.1016/j.bbamcr.2012.06.019
• Collins, K. (2016). Determining the role of Mtm1 in Glutathione metabolism. South Carolina Junior Academy of Science. 9. https://scholarexchange.furman.edu/scjas/2016/all/9
• Danneman, B., Lehle, S., Hildebrand, D.G., Kübler, A., Grodona, P., Schmid, V., Holzer, K., Fröschl, M., Essmann, F., Rothfuss, O., & Osthoff, K.S. (2015). High glutathione and glutathione peroxidase-2 levels mediate cell-type-specific DNA damage protection in human iInduced pluripotent stem cells. Stem Cell Reports, 4(5), 886–898. https://doi.org/10.1016/j.stemcr.2015.04.004
• El Osta, H. & Circu, M.L. (2016). Mitochondrial ROS and apoptosis. Mitochondrial Mechanisms of Degeneration and Repair in Parkinson’s Disease, 1 23. https://doi.org/10.1007/978-3-319-42139-1_1
• Esteve, J.M., Mompo J., García de la Asunción, J., Sastre J., Asensi, M., Boix, J., Viña, J.R., Viña, J., Pallardo, F.V. (1999). Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro. Federation of American Socities for Experimental Biology, 13, 1055–1064. https://doi.org/10.1096/fasebj.13.9.1055
• Flagg, E.W., Coates, R.J., Eley, J.W., & Jones, D.P., Gunter, E.W., Byers, T.E., Block, G.S., Greenberg, R.S. (1994). Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level. Nutrition and Cancer, 21(1), 33-46. https://doi.org/10.1080/01635589409514302
• Franco, R., Panayiotidis, M.I., & Cidlowski, J.A. (2007). Glutathione depletion is necessary for apoptosis in lymphoid cells independent of reactive oxygen species formation. Journal of Biological Chemistry, 282, 30452–30465. https://doi.org/10.1074/jbc.M703091200
• Fucassi, F., Lowe, J.E., Pavey, K.D., Shah, S., Faragher, R.G.A., Green, M.H.L., Paul, F., O’Hare, D., & Cragg, P.J. (2006). Alpha-ipoic acid and glutathione protect against the prooxidant activity of SOD/catalase mimetic manganese salen derivatives. Journal of Inorganic Biochemistry, 101, 225–232. https://doi.org/10.1016/j.jinorgbio.2006.09.023
• Garvey, T.Q., Hyman, P.E. & Isselbacher, K.J. (1976). γ-Glutamyl transpeptidase of rat intestine: Localization and possible role in amino acid transport. Gastroenterology, 71(5), 778–785. https://doi.org/10.1016/S0016-5085(76)80360-5
• Giustarindi, D., Tsikas, D., Colombo, G., Milzani, A., Donne, I.D., Fanti, P., & Rossi, R. (2016). Pitfalls the analysis of the physiological antioxidant glutathione (GSH) and its disulfide (GSSG) in biological samples: An elephant in the room. Journal of Chromatography B, 1019, 21-28. https://doi.org/10.1016/j.jchromb.2016.02.015
• Hagen, T.M., Wierzbicka, G.T., Sillau, A.H., Bowman, B.B., & Jones, D.P. (1990). Bioavailability of dietary glutathione: effect on plasma concentration. American Journal of Physiological, 259(4), 524-9. https://doi.org/10.1152/ajpgi.1990.259.4.g524
• Halliwell, B. (2013). The antioxidant paradox: Less paradoxical now? British Journal of Clinical Pharmacology, 75(3), 637 644. https://doi.org/10.1111/J.1365 2125.2012.04272.X
• Iantomasi, T., Favilli, F., Marraccini, P., Magaldi, T., Bruni, P., & Vincenzini, M.T. (1997). Glutathione transport system in human small intestine epithelial cells. Biochimica et Biophysica Acta, 1330(2), 274-83. https://doi.org/10.1016/s0005-2736(97)00097-7
• Ighodaro, O.M., & Akinloye, O.A. (2018). First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine, 54(4), 287-93. https://doi.org/10.1016/j.ajme.2017.09.001
• Jain, S.K., Marie, P.K., Warden, C., & Micinski, D. (2016). L-cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats. Molecular Nutrition Food Research, 60, 1090–1098. https://doi.org/10.1002/mnfr.201500667
• Kannan, R., Yi, J.R., Tang, D., Zlokovic, B.V., & Kaplowitz, N. (1996). Identification of a novel, sodium-dependent, reduced glutathione transporter in the rat lens epithelium. Investigative Ophthalmol and Visual Science, 37(11), 2269 2275. https://iovs.arvojournals.org/article.aspx?articleid=2180347
• Kern, J.K., Geier, D.A., Adams, J.B., Garver, C.R., Audhya, T., & Geier, M.R. (2011). A clinical trial of glutathione supplementation in autism spectrum disorders. Medical Science Monitor, 17(12), 677-682. https://doi.org/10.12659/msm.882125
• Lim, H, Bodmer, R., & Perrin, L. (2006). Drosophila aging 2005/06. Experimental Gerontology, 41, 1213-1216. https://doi.org/10.1016/j.exger.2006.10.013
• Mannarino, S.C., Amorim, M.A., Pereira, M.D., Moradas-Ferreira, P., Panek, A.D., Costa, V., & Eleutherio, E.C.A. (2008). Glutathione is necessary to ensure benefits of calorie restriction during ageing in Saccharomyces cerevisiae. Mechanisms of Ageing and Development, 129, 700–705. https://doi.org/10.1016/j.mad.2008.09.001
• Marengo, B., De Ciucis, C., Verzola, D., Pistoia, V., Raffaghello, L., Patriarca, S., Balbis, E., Traverso, N., Cottalasso, D., Pronzato, M.A., Marinari, U.M., & Domenicotti, C. (2008). Mechanisms of BSO (L-buthionine-S, R-sulfoximine)-induced cytotoxic effects in neuroblastoma. Free Radical Biology and Medicine, 44, 474 482. https://doi.org/10.1016/j.freeradbiomed.2007.10.031
• Meister, A. (1991). Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacology and Therapeutics, 51(2), 155-194. https://doi.org/10.1016/0163-7258(91)90076-x
• Min, K.H, & Lee, W. (2019). Alteration of mitochondrial DNA content modulates antioxidant enzyme expressions and oxidative stress in myoblasts. Korean Journal of Physiology Pharmacology, 23, 519-528. https://doi.org/10.4196/kjpp.2019.23.6.519
• Minich, D.M., & Brown, B.I. (2019). A review of dietary (Phyto) nutrients for glutathione support. Nutrients, 11(9), E2073. https://doi.org/10.3390/nu11092073
• Mutlu, A.G. (2012a). Increase in mitochondrial DNA copy number in response to ochratoxin A and methanol-induced mitochondrial DNA damage in drosophila. Bulletin of Environmental Contamination and Toxicology, 89, 1129 1132. https://doi.org/10.1007/s00128-012-0826-1
• Mutlu, A.G. (2012b). Measuring of DNA damage by quantitative PCR, pp. 283-294. Polymerase Chain Reaction, Patricia Hernandez-Rodriguez, In tech, Rijeka, Croatia. https://doi.org/10.5772/38159
• Mutlu, A.G. (2013). The effects of a wheat germ rich diet on oxidative mtDNA damage, mtDNA copy number and antioxidant enzyme activities in aging Drosophila. Acta Biologica Hungarica, 64(1),1-9. https://doi.org/10.1556/abiol.64.2013.1.1
• Owen, J.B., & Butterfield, D.A. (2010). Measurement of oxidized/reduced glutathione ratio. Methods in Molecular Biology, 648, 269-277. https://doi.org/10.1007/978-1-60761-756-3_18
• Pallardó, F.V., Markovic, J., García, J.L., & Viña, J. (2009). Role of nuclear glutathione as a key regulator of cell proliferation. Molecular Aspects of Medicine, 30, 77–85. https://doi.org/10.1016/j.mam.2009.01.001
• Rebrin, I., Kamzalov, S., & Sohal, R.S., (2003). Effects of age and caloric restriction on glutathione redox state in mice. Free Radical Biology and Medicine, 35(6), 626–635. https://doi.org/10.1016/S0891-5849(03)00388-5
• Rebrin, I., & Sohal, R. S. (2008). Pro-oxidant shift in glutathione redox state during aging. Advanced Drug Delivery Reviews, 60(13 14), 1545 1552. https://doi.org/10.1016/J.ADDR.2008.06.001
• Richie, J.J., Nichenametla, S., Neidig, W., Calcagnotto, A., Haley, J.S., Schell, T.D., & Muscat, J.E. (2014). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition, 54(2), 251-263. https://doi.org/10.1007/s00394-015-0874-5
• Santos, J.H., Mandavilli, B.S., & Van Houten, B. (2002). Measuring oxidative mtDNA damage and repair using QPCR. In: Copeland WC (ed) Mitochondrial DNA methods and protocols. Humana Press, Totawa, pp 159–176. https://doi.org/10.1385/1-59259-284-8:159
• Shaw, P., Ocorr, K., Bodmer, R., Oldham, S. (2008). Drosophila aging 2006/2007. Experimental Gerontology, 43, 5-10. https://doi.org/10.1016/j.exger.2007.10.008
• Sheshadri, P., & Kumar A., (2016). Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD. Free Radical Research, 50(5), 570-84. https://doi.org/10.3109/10715762.2016.1155708
• Solov’eva, M.E., Solov’ev, V.V., Faskhutdinova, A.A., Kudryavtsev, A.A., & Akatov, V.S. (2007). Prooxidant and cytotoxic action of N-Acetylcysteine and Glutathione in combinations with Vit B12. Cell and Tissue Biology, 1, 40 49. https://doi.org/10.1134/S1990519X07010063
• Sze, G., Kaplowitz, N., Ookhtens, M., & Lu, S.C. (1993). Bidirectional membrane transport of intact glutathione in Hep G2 cells. American Journal of Physiology, 265(6), 1128 34. https://doi.org/10.1152/ajpgi.1993.265.6.g1128
• Venkatraman, A., Landar, A., Davis, A.J., Chamlee, L., Sandersoni, T., Kim, H., Page, G., Pompilius, M., Ballinger, S., Darley-Usmar, V., & Bailey, S.M. (2004). Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatoxicity. Journal of Biological Chemistry, 279, 22092–101. https://doi.org/10.1074/jbc.m402245200
• Weschawalit, S., Thongthip, S., Phutrakool, P., & Asawanonda, P. (2017). Glutathione and its antiaging and antimelanogenic effects. Clinical Cosmetic Investigional Dermatology, 10, 147–153. https://doi.org/10.2147/ccid.s128339
• Witschi, A., Reddy, S., Stofer, B., & Lauterburg, B.H. (1992). The systemic availability of oral glutathione. European Journal of Clinical Pharmacology, 43(6), 667 669. https://doi.org/10.1007/BF02284971
• Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R., & Turner, N.D. (2004). Glutathione metabolism and its implications for health. Journal of Nutrition, 134(3), 489 492. https://doi.org/10.1093/jn/134.3.489
• Yakes, F.M., & Van Houten, B. (1997). Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proceedings of the National Academy Sciences of the United States of America, 94, 514-519. https://doi.org/10.1073/pnas.94.2.514