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

Juliet M Taylor1, Peter J Crack, Jodee A Gould

  • 1Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.

Experimental Cell Research
|October 12, 2004
PubMed

Insights

Glutathione peroxidase 1 (Gpx1) deficiency increases cell death from hydrogen peroxide (H2O2) by reducing the PI(3)K-Akt survival pathway, despite activating NFkappaB. These pathways operate independently in oxidative stress.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Oxidative stress is implicated in numerous diseases.
  • Endogenous antioxidants, like glutathione peroxidase 1 (Gpx1), protect cells from oxidative damage.
  • Understanding the molecular mechanisms of oxidative stress-induced cell death is crucial.

Purpose of the Study:

  • To investigate the role of Gpx1 in cellular response to oxidative stress.
  • To elucidate the involvement of the PI(3)K-Akt and NFkappaB pathways in Gpx1-deficient cells under oxidative conditions.

Main Methods:

  • Utilized Gpx1 knockout (Gpx1-/-) and wild-type cells.
  • Exposed cells to exogenous hydrogen peroxide (H2O2).
  • Assessed cell death (apoptosis) and activation of the PI(3)K-Akt and NFkappaB pathways.

Main Results:

  • Gpx1-/- cells exhibited increased apoptosis upon H2O2 treatment compared to wild-type cells.
  • This heightened cell death correlated with decreased activation of the PI(3)K-Akt survival pathway in Gpx1-/- cells.
  • NFkappaB activation was elevated in Gpx1-/- cells, and could be further increased by inhibiting Akt in wild-type cells.

Conclusions:

  • Diminished PI(3)K-Akt pathway activation contributes to increased susceptibility to H2O2-induced apoptosis in Gpx1-/- cells.
  • The NFkappaB pathway remains activated in Gpx1-/- cells, suggesting independent operation from the Akt pathway.
  • These findings highlight the distinct roles of PI(3)K-Akt and NFkappaB in managing endogenous oxidative stress.

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