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Redox regulation of the tumor suppressor PTEN by the thioredoxin system and cumene hydroperoxide

Title
Redox regulation of the tumor suppressor PTEN by the thioredoxin system and cumene hydroperoxide
Authors
Han S.-J.Zhang Y.Kim I.Chay K.-O.Yoon H.J.Jang D.I.Yang S.Y.Park J.Woo H.A.Park I.Lee S.-R.
Ewha Authors
최병일Jennifer Sejin Oh
SCOPUS Author ID
최병일scopus; Jennifer Sejin Ohscopus
Issue Date
2017
Journal Title
Free Radical Biology and Medicine
ISSN
0891-5849JCR Link
Citation
vol. 112, pp. 277 - 286
Keywords
Cumene hydroperoxidePTENReactive oxygen speciesRedox signalingThioredoxin
Publisher
Elsevier Inc.
Indexed
SCI; SCIE; SCOPUS scopus
Abstract
Intracellular redox status influences the oxidation and enzyme activity of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN). Cumene hydroperoxide (CuHP), an organic hydroperoxide, is a known tumor promoter. However, molecular targets and action mechanism of CuHP in tumor promotion have not been well characterized. 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 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 CuHP in HeLa cells. A combination of protein fractionation and mass analysis showed that the reducing system of PTEN was 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 exogenous Trx system, indicating that the cellular Trx redox system for PTEN is inactivated by CuHP. We present evidence that PTEN oxidation and the concomitant inhibition of thioredoxin by CuHP results in 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 hydroperoxides. © 2017
DOI
10.1016/j.freeradbiomed.2017.07.029
Appears in Collections:
국제대학원 > 국제학과 > Journal papers
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