Altered glutamate cysteine ligase activity in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

Abstract

Reductions in glutathione (GSH) levels have been shown to be associated with aging and the pathogenesis of a variety of diseases, including systemic lupus erythematosus (SLE). Glutamate cysteine ligase (GCL) catalyzes the first and rate-limiting step of GSH synthesis. In order to appraise the correlation between oxidative stress and the severity and activity of SLE, GSH, oxidized GSH (GSSG) and thioredoxin (TRX) concentrations and the enzymatic activity levels of GCL in peripheral blood mononuclear cells (PBMCs) from patients with SLE and healthy controls were studied. In patients with SLE, the levels of GCL activity and GSH decreased, while TRX and GSSG levels increased when compared with those in the healthy controls. GSH concentrations and GCL activity levels negatively correlated with the SLE disease activity index and erythrocyte sedimentation rate. Furthermore, patients with SLE and nephritis had lower levels of GSH and GCL activity and higher levels of TRX and GSSG compared with those in SLE patients without nephritis. Therefore, the results of the present study indicate that insufficient levels of GSH and GCL activity in PBMCs may contribute to the pathogenesis of SLE.