Gamma-glutamyltransferase is upregulated after oxidative stress through the Ras signal transduction pathway in rat colon carcinoma cells.

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 Res

journal_title

Free radical research

authors

Pandur S,Pankiv S,Johannessen M,Moens U,Huseby NE

doi

10.1080/10715760701739488

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1376-84

issue

12

eissn

1071-5762

issn

1029-2470

pii

783886140

journal_volume

41

pub_type

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