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The effects of modulation of gamma-glutamyl transpeptidase activity in HepG2 cells on thiol homeostasis and caspase-3-activity.

Abstract
The present studies aimed to elucidate how the modulation of gamma-glutamyl transpeptidase (gammaGT) activity in human hepatoma (HepG2) cell line influences H(2)O(2) production, caspase 3 activity, protein S-thiolation by glutathione (GSH), cysteinyl-glycine (Cys-Gly) and cysteine (Cys), and the level of other redox forms of these thiols. The experiments showed that 1-h stimulation of gammaGT elevated H(2)O(2) production, leading to prooxidant conditions. After 24-h stimulation, H(2)O(2) concentration was at the control level, while Cys-Gly-, Cys- and GSH-dependent S-thiolation was markedly increased, which was accompanied by a drop in caspase-3 activity. The inhibition of gammaGT activity by acivicin led to H(2)O(2) decrease after 1-h incubation which still persisted after 24 h. The inhibition of gammaGT activity in HepG2 cells was also connected with the lowering of S-thiolation with Cys and Cys-Gly and with increasing of caspase-3 activity. The results of our studies indicate that the modulation of gammaGT activity can be used to change cellular redox status, and can affect Cys- and Cys-Gly-dependent S-thiolation and caspase-3 activity. We suggest that the role of high gammaGT activity in HepG2 cells can be connected with production of reactive oxygen species and with S-thiolation with Cys and Cys-Gly that can influence activity of caspase 3.
AuthorsMałgorzata Iciek, Grazyna Chwatko, Hanna Rokita, Edward Bald, Lidia Włodek
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1773 Issue 2 Pg. 201-8 (Feb 2007) ISSN: 0006-3002 [Print] Netherlands
PMID17141888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dipeptides
  • Disulfides
  • Enzyme Inhibitors
  • Sulfhydryl Compounds
  • cysteinylglycine
  • Hydrogen Peroxide
  • gamma-Glutamyltransferase
  • Caspase 3
  • Glutathione
  • Cysteine
Topics
  • Caspase 3 (metabolism)
  • Catalysis
  • Cell Death
  • Cell Line, Tumor
  • Cysteine (analysis, metabolism)
  • Dipeptides (analysis, metabolism)
  • Disulfides (metabolism)
  • Enzyme Activation
  • Enzyme Inhibitors (pharmacology)
  • Glutathione (analysis, metabolism)
  • Homeostasis
  • Humans
  • Hydrogen Peroxide (metabolism)
  • Oxidation-Reduction
  • Sulfhydryl Compounds (analysis, metabolism)
  • gamma-Glutamyltransferase (antagonists & inhibitors, metabolism)

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