Peroxiredoxin 3 has important roles on arsenic trioxide induced apoptosis in human acute promyelocytic leukemia cell line via hyperoxidation of mitochondrial specific reactive oxygen species

Yeung Chul Mun, Jee Young Ahn, Eun Sun Yoo, Kyoung Eun Lee, Eun Mi Nam, Jungwon Huh, Hyun Ae Woo, Sue Goo Rhee, Chu Myong Seong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2’, 7’-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX™ Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO2 (Cysteine sulfinic acid, Cys–SO2 H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO2 form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

Original languageEnglish
Pages (from-to)813-820
Number of pages8
JournalMolecules and Cells
Volume43
Issue number9
DOIs
StatePublished - 30 Sep 2020

Keywords

  • Acute promyelocytic leukemia
  • Arsenic trioxide
  • Peroxiredoxin 3

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