Gamma-Glutamylcysteine Inhibits Oxidative Stress in Human Endothelial Cells.

摘要

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 PPAR(gamma) DNA binding and lower levels of GSH, GSS protein, NF-(kappa)B p65 DNA binding, thiobarbituric acid reactive substances (TBARS), and 8-epi-PGF2(alpha) in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPAR(gamma) DNA binding levels and positive correlation trends with NF-(kappa)B p65DNA binding, TBARS, and 8-epi-PGF2(alpha) levels. A putative binding site for NF-(kappa)B 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-(kappa)B 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 protein(s) 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.