Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis

N. Montesano Gesualdi, G. Chirico, G. Pirozzi, E. Costantino, M. Landriscina, F. Esposito

Research output: Contribution to journalArticle

Abstract

TRAP-1 is a mitochondrial heat shock protein (HSP), recently identified in Saos-2 osteosarcoma cells adapted to mild oxidative stress induced by diethylmaleate (DEM). TRAP-1 mRNA expression is increased in DEM-adapted cells as well as in tumor cells resistant to 5-fluorouracil and to platin derivatives. Since a strong decrease of TRAP-1 protein levels, upon cisplatin treatment, is observed only in controls but not in the DEM-adapted counterpart, a possible role for this protein in the development of resistant phenotypes could be hypothesized. To characterize the protective role of TRAP-1 against oxidative stress and apoptosis, stable transfectants were generated and characterized for their response to different stress types. These stable clones expressing constitutively high TRAP-1 levels: (i) are more resistant to H2O2-induced DNA damage and to apoptosis by cisplatin; (ii) contain higher reduced glutathione (GSH) levels than control cells; and (iii) do not release the apoptosis-inducing factor into the nucleus upon cisplatin treatment. Furthermore, high TRAP-1 levels interfere with caspase 3 activation. These results confirm the anti-apoptotic role of TRAP-1, and suggest that increased expression of this mitochondrial HSP in DEM-adapted and chemoresistant cells could be part of a pro-survival signaling pathway aimed to evade toxic effects of oxidants and anticancer drugs.

Original languageEnglish
Pages (from-to)342-350
Number of pages9
JournalStress
Volume10
Issue number4
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Apoptosis
  • Chemoresistance
  • Heat shock protein 75
  • Osteosarcoma
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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  • Cite this

    Gesualdi, N. M., Chirico, G., Pirozzi, G., Costantino, E., Landriscina, M., & Esposito, F. (2007). Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis. Stress, 10(4), 342-350. https://doi.org/10.1080/10253890701314863