Glutathione turnover in human cell lines in the presence of agents with glutathione influencing potential with and without acivicin inhibition of gamma-glutamyltranspeptidase.

Summary, in English

Background: We have previously shown that there were great discrepancies between different agents regarding their glutathione stimulating potential and that agents with mainly oxidative effects did not increase concentrations of glutathione in human cell cultures, in contrast to other thiol reactive agents. In order to evaluate whether increased glutathione degradation might be one reason for these discrepancies, we have investigated the effect of different agents with potential influence on glutathione metabolism in human cell cultures with or without acivicin inhibition of gamma-glutamyltranspeptidase (GT), since GT is responsible for the initial degradation of glutathione. Methods: Intra- and extracellular concentrations of glutathione were investigated in HeLa and hepatoma cell cultures, with and without acivicin inhibition of GT, in the presence of oxidative and electrophilic agents (copper ions, hydrogen peroxide and N-ethylmaleimide), hydroquitione, reducing agents (lipoic acid and N-acetylcysteine), and a thiol reactive metal (mercury ions). Results: There were great discrepancies between the different agents regarding their maximal glutathione response (the sum of the intracellular and the extracellular amount of glutathione) in cell cultures. There was only a small increase in total glutathione in the presence of hydrogen peroxide or N-ethylmaleimide before the cell protein decreased compared to findings with mercury ions, lipoic acid or hydroquinone. In both HeLa and hepatoma cell cultures, there were correlations between the original glutathione amount and the total glutathione amount observed after acivicin inhibition. Conclusion: The relatively small increase of glutathione amount in the presence of oxidative and electrophilic agents compared to other thiol reactive agents is not due to increased GT degradation of glutathione.

• Författare: Malin Hultberg; Björn Hultberg
• Avdelning/ar: Avdelningen för klinisk kemi och farmakologi
• Publiceringsår: 2005
• Språk: Engelska
• Sidor: 42-47
• Publikation/Tidskrift/Serie: Biochimica et Biophysica Acta. General Subjects
• Volym: 1726
• Issue: 1
• Länkar: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16216418&dopt=Abstract; http://dx.doi.org/10.1016/j.bbagen.2005.08.007
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Pharmacology and Toxicology; Medicinal Chemistry
• Nyckelord: mercury ion; gamma-glutamyltranspeptidase; electrophilic agent; glutathione; human; cell line; oxidative agent
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0304-4165