Redox Regulation of the Tumor Suppressor PTEN by the Thioredoxin System and Cumene Hydroperoxide.

In this study, we investigated the effect of CuHP on the redox state of PTEN in HeLa cells. In addition, the intracellular reducing system of oxidized PTEN was analyzed by using a biochemical approach and the effect of CuHP on this reducing system was also analyzed. While PTEN oxidized by hydrogen peroxide is progressively converted to its reduced form, PTEN was irreversibly oxidized by exposure to cumene hydroperoxide (CuHP) in HeLa cells. A combination of protein fractionation and mass analysis identified the reducing system of PTEN comprised of NADPH, thioredoxin reductase (TrxR) and thioredoxin (Trx). Although CuHP-mediated PTEN oxidation was not reversible in cells, CuHP-oxidized PTEN was reactivated by the Trx system in vitro, indicating that the cellular Trx redox system for PTEN is inactivated by CuHP. We present evidence that PTEN oxidation and concomitant inhibition of thioredoxin by CuHP result in the irreversible oxidation of PTEN in HeLa cells. In addition, ablation of peroxiredoxin (Prdx) enhanced CuHP-induced PTEN oxidation in cells. These results provide a new line of evidence that PTEN might be a crucial determinant of cell fate in response to cellular oxidative stress induced by organic hydroperoxide. PMID: 28774816 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research