Peroxiredoxin III Protects Tumor Suppressor PTEN from Oxidation by 15-Hydroperoxy-eicosatetraenoic Acid

Abstract EN

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase that coordinates various cellular processes.

Its activity is regulated by the reversible oxidation of an active-site cysteine residue by H2O2 and thioredoxin.

However, the potential role of lipid peroxides in the redox regulation of PTEN remains obscure.

To evaluate this, 15-hydroperoxy-eicosatetraenoic acid (15s-HpETE), a lipid peroxide, was employed to investigate its effect on PTEN using molecular and cellular-based assays.

Exposure to 15s-HpETE resulted in the oxidation of recombinant PTEN.

Reversible oxidation of PTEN was also observed in mouse embryonic fibroblast (MEF) cells treated with a 15s-HpETE and Lipofectamine mixture.

The oxidative dimerization of thioredoxin was found simultaneously.

In addition, the absence of peroxiredoxin III aggravated 15s-HpETE-induced PTEN oxidation in MEF cells.

Our study provides novel insight into the mechanism linking lipid peroxidation to the etiology of tumorigenesis.