Protective role of cytosolic 2-cys peroxiredoxin in the TNF-α-induced apoptotic death of human cancer cells

Joo Young Lee, Hyung Jung Jung, In Sung Song, Mark S. Williams, Chulhee Choi, Sue Goo Rhee, Jiyoung Kim, Sang Won Kang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Cytosolic 2-cys peroxiredoxin (2-cysPrx) exhibiting thioredoxin-dependent hydroperoxide reductase activity has been demonstrated to be involved in a number of signaling processes, such as receptor tyrosine kinase and MAP kinase activation. However, its role in the cell death pathway has yet to be elucidated. Here we show that cytosolic 2-cysPrx suppresses the TNF-α-induced apoptosis of human cervical cancer cells in a caspase-8-dependent manner. The HeLa cervical cancer cells expressing a dominant negative mutant (DN) of a cytosolic 2-cysPrx manifested remarkable increase in intracellular reactive oxygen species level, which was counteracted by catalase administration, and apoptotic cell death induced by combined treatment of TNF-α and cycloheximide compared to the control (CT) cells. Similarly, the DN cells were also susceptible to apoptosis induced by the TNF-related apoptosis-inducing ligand. The apoptosis enhanced by DN expression was shown to be dependent on a typical FADD/caspase pathway. The DN cells undergoing apoptosis showed enhanced caspase-8 and -3 activations, as compared to the CT cells. In contrast, there was no difference observed in the sustained JNK activation between CT and DN cells. Thus, this study illustrates that intracellular reactive oxygen species regulated by cytosolic 2-cysPrx is involved in the TNF-α-induced apoptotic cell death via controlling caspase activation.

Original languageEnglish
Pages (from-to)1162-1171
Number of pages10
JournalFree Radical Biology and Medicine
Volume47
Issue number8
DOIs
StatePublished - 15 Oct 2009

Keywords

  • 2-cys peroxiredoxin
  • Apoptosis
  • Caspase
  • Reactive oxygen species
  • Tumor necrosis factor-α

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