Effect of Cyclosporine A on the expression of GSTO2 metabolizing enzyme in Jurkat cell line

Abstract

A B S T R A C T 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. Th e 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 radical s induced by CsA.