title: γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We assessed oxidative stress, GSH, GSH synthetase (GSS) expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells (HUVEC).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition, University of Nevada, Reno 89557, USA.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Nakamura
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: Stanley T
authors.initials: ST
authors.lastname: Omaye
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004151:Dipeptides / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D004151:Dipeptides; D005978:Glutathione; C017341:gamma-glutamylcysteine