Gamma-Glutamylcysteine Inhibits Oxidative Stress in Human Endothelial Cells

Aims gamma-Glutamylcysteine GGC is a dipeptide and substrate for synthesis of the antioxidant glutathione GSH, whose health promoting properties include reducing risks of oxidative stress-related injuries and diseases. The objective of this study was to investigate the efficacy of GGC on GSH synthesis and oxidative stress in human endothelial cells. Main methods We assessed oxidative stress, GSH, GSH synthetase GSS expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells HUVEC. Key findings We found significantly higher levels of PPARgamma DNA binding and lower levels of GSH, GSS protein, NF-kappaB p65 DNA binding, thiobarbituric acid reactive substances TBARS, and 8-epi-PGF2alpha in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPARgamma DNA binding levels and positive correlation trends with NF-kappaB p65DNA binding, TBARS, and 8-epi-PGF2alpha levels. A putative binding site for NF-kappaB was found at 4 227 bases upstream from the transcription start site of GSS gene, but none for PPARs. These findings suggest the involvement of NF-kappaB in regulation of GSS expression. Subsequent GSH synthesis might be affected by the suppression of GSS expression in tested conditions. Significance Besides its substrate role in GSH synthesis, GGC may play a role in protection against oxidative stress by serving as an antioxidant and modulating the expression of proteins related to antioxidant defense. Thus, we speculate that GGC may serve as a novel intra- and intercellular therapeutic dipeptide for oxidative stress-related injuries and diseases.