Purine derivatives such as caffeine and uric acid have neuroprotective activities and reduce the risk of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. We have reported that caffeine, uric acid and paraxanthine, a major metabolite of caffeine, promote cysteine uptake in hippocampal slices. We have also reported that paraxanthine promotes the cysteine uptake and the synthesis of intracellular antioxidant molecule, glutathione (GSH), in HEK293 cells.
In this study, we examined the effect of uric acid, an end-product of purine metabolism, on cysteine uptake and GSH synthesis in HEK293 cells. Uric acid was treated to HEK293 cells for 30min at concentrations of 0, 10 and 100 μM in cystine-deprived condition, and then cysteine was added for 30 min at concentrations of 100 and 400 µM. High performance liquid chromatography analysis showed that uric acid decreased the extracellular cysteine levels. Fluorescent GSH detection by CMFDA indicated that uric acid increased intracellular GSH levels. These results suggest that uric acid promotes cysteine uptake leading to GSH synthesis in HEK293 cells.