Akt phosphorylation and NFκB activation are counterregulated under conditions of oxidative stress

Juliet M. Taylor, Peter J. Crack, Jodee A. Gould, Uǧur Ali, Paul J. Hertzog, Rocco C. Iannello

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

This study was designed to elucidate the mechanisms involved in elevated cell death arising from an altered endogenous oxidant state. Increased levels of cell death were detected in cells lacking Gpx1 following the addition of exogenous H2O2. This increased apoptosis correlated with a down-regulation in the activation of the PI(3)K-Akt survival pathway. The importance of this pathway in protecting against H2 O 2-induced cell death was highlighted by the increased susceptibility of wild-type cells to apoptosis when treated with the PI(3)K inhibitor, LY294002. Activation of the oxidative stress sensitive transcription factor, NFκB, was elevated in the Gpx1-/- cells. Significantly, NFκB activation could be increased in wild-type cells through the addition of dominant-negative Akt. Therefore, our results suggest that the increased susceptibility of Gpx1-/- cells to H2O2-induced apoptosis can be attributed in part to diminished activation of Akt despite an up-regulation in the activation of the prosurvival NFκB. Thus, the PI(3)K-Akt and NFκB pathways can act independently of each other in an endogenous model of oxidative stress.

Original languageEnglish
Pages (from-to)463-475
Number of pages13
JournalExperimental Cell Research
Volume300
Issue number2
DOIs
Publication statusPublished - 1 Nov 2004

Keywords

  • Akt
  • Apoptosis
  • Gpx1
  • NFκB
  • Oxidative stress

Cite this