Cyclosporine A (CsA), a cyclic polypeptide metabolite extracted from the fungus, is used clinically to combat organ graft rejection in transplant subjects. Previous studies have shown that CsA exposure enhances the production of reactive oxygen species (ROS) and lipid peroxidation, which are directly involved in CsA toxicity. To protect cells and organs against ROS, the human body has evolved a highly antioxidant protection system to neutralize free radicals. The aim of this study was to investigate the effect of CsA on mRNA expression of anti-oxidant GSTO2. To do this, Jurkat cells were incubated for 24 h with different doses of CsA, ranging from 1-80 µg/ml, and the IC50 of CsA was calculated to be 40 µg/ml. Subsequently, Jurkat cells were treated with 3 µg/ml CsA for 24 h and the gene expression of GSTO2 was quantified by quantitative Real-time PCR. Results showed that the mean (SD) expression of the GSTO2 gene in CsA treated cells was 1.10 (0.07) (when assuming an expression level in untreated cells of 1.0). However, statistical analyses showed that the alterations were not significant (t=2.29, df=2, P=0.149). These findings suggest that at this concentration of CsA, other antioxidant enzymes are up-regulated in Jurkat cell lines to detoxify free radicals induced by CsA.
Kahan BD. Cyclosporine: arevolution in transplantation. Transplant Proc 1999;31:14S-15S.
Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR. Identification of a putative regulator of early T cell activation genes. Science 1998;241:202-205.
Yoshimura N, Okamoto M, Akioka K, Kaihara S. Optimization of the use of cyclosporine in renal transplantation. Transplant Proc 2004;36:181S-185S.
Kahan BD, Flechner SM, Lorber MI, Golden D, Conley S, Van Buren CT. Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. Transplantation 1987;43:197-204.
Bach JF. The contribution of cyclosporine A to the understanding and treatment of autoimmune diseases. Transplant Proc 1999;31:16S-18S.
Muellenhoff MW, Koo JY. Cyclosporine and skin cancer: an international dermatologic perspective over 25 years of experience. A comprehensive review and pursuit to define safe use of cyclosporine in dermatology. J Dermatolog Treat 2011;23:290-304.
Haw S, Shin MK, Haw CR. The efficacy and safety of long-term oral cyclosporine treatment for patients with atopic dermatitis. Ann Dermatol 2010;22:9-15.
Kavanagh GM, Ross JS, Cronin E, Smith NP, Black MM. Recalcitrant pyoderma gangrenosum--two cases successfully treated with cyclosporin A. Clin Exp Dermatol 1992; 17:49-52.
Pham CQ, Efros CB, Berardi RR. Cyclosporine for severe ulcerative colitis. Ann Pharmacother 2006;40:96-101.
Utine CA, Stern M, Akpek EK. Clinical review: topical ophthalmic use of cyclosporin A. Ocul Immunol Inflamm 2010;18:352-61.
De Mattos AM, Olyaei AJ, Bennett WM. Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am J Kidney Dis 2000;35:333-346.
Olyaei AJ, de Mattos AM, Bennett WM. Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care 2001;7:384-389.
Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney Int 1994:45:1-9.
Stroes ESG, Lue Scher TF, De Groot FG, Koomans HA, Rabelink, TJ. Cyclosporin A increases nitric oxide activity in vivo. Hypertension 1997;29:570-575.
Ahmed SS, Strobel HW, Napoli KL, Grevel J. Adrenochrome reaction implicates oxygen radicals in metabolism of cyclosporine A and FK-506 in rat and human liver microsomes. J Pharmacol Exp Ther 1993;265:1047-1054.
Wang C, Salahudeen AK. Lipid peroxidation accompanies cyclosporine nephrotoxicity: effects of vitamin E. Kidney Int 1995;47:927-934.
Paller MS. Free radical scavengers in mercury chloride-induced acute renal failure in the rat. J Lab Clin Med 1985;105:459-463.
Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol 2002;137:771-781.
Nebert DW, Vasiliou V. Analysis of the glutathione S-transferase (GST) gene family. Hum Genomics 2004;1:460-464.
Rezzani R. Exploring cyclosporine A: Side effects and the protective role-played by antioxidants: the morphological and immunehistochemical studies. Histol Histopathol 2006; 21:301-316.
Nekooie-Marnany, N., & Saadat, I. (2012). Effect of Cyclosporine A on the expression of GSTO2 metabolizing enzyme in Jurkat cell line. Molecular Biology Research Communications, 1(1), 16-20. doi: 10.22099/mbrc.2012.236
MLA
Nioosha Nekooie-Marnany; Iraj Saadat. "Effect of Cyclosporine A on the expression of GSTO2 metabolizing enzyme in Jurkat cell line", Molecular Biology Research Communications, 1, 1, 2012, 16-20. doi: 10.22099/mbrc.2012.236
HARVARD
Nekooie-Marnany, N., Saadat, I. (2012). 'Effect of Cyclosporine A on the expression of GSTO2 metabolizing enzyme in Jurkat cell line', Molecular Biology Research Communications, 1(1), pp. 16-20. doi: 10.22099/mbrc.2012.236
VANCOUVER
Nekooie-Marnany, N., Saadat, I. Effect of Cyclosporine A on the expression of GSTO2 metabolizing enzyme in Jurkat cell line. Molecular Biology Research Communications, 2012; 1(1): 16-20. doi: 10.22099/mbrc.2012.236