γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells

Abstract

Aims: γ-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 PPARγ DNA binding and lower levels of GSH, GSS protein, NF-κB p65 DNA binding, thiobarbituric acid reactive substances (TBARS), and 8-epi-PGF(2α) in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPARγ DNA binding levels and positive correlation trends with NF-κB p65 DNA binding, TBARS, and 8-epi-PGF(2α) levels. A putative binding site for NF-κB 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-κB 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.