Abstract:
:Gamma-glutamyltransferase (GGT) plays a central role in the homeostasis of the antioxidant glutathione (GSH). The expression of GGT has been shown to be upregulated after oxidative stress, but the signalling pathways implicated remain poorly characterized. The results here show that acute exposure of CC531 cells to oxidative stress resulted in activation of Ras and augmented GGT enzyme activity, both at the transcriptional and at the translation level. Moreover, an involvement of the GGT promoter II was detected after RT-PCR and transient transfection studies. Ectopic expression of activated Ras, but not dominant negative Ras, also resulted in increased GGT promoter II transcriptional activity, an effect that was attenuated by over-expression of dominant negative mutants of Akt, p38 MAPK and MEK1. Addition of specific inhibitors of these kinases during oxidative stress diminished the activation of GGT. In conclusion, oxidative stress-induced activation of GGT involves Ras and several downstream signalling pathways.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Pandur S,Pankiv S,Johannessen M,Moens U,Huseby NEdoi
10.1080/10715760701739488subject
Has Abstractpub_date
2007-12-01 00:00:00pages
1376-84issue
12eissn
1071-5762issn
1029-2470pii
783886140journal_volume
41pub_type
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