Upregulation of thioredoxin and its reductase attenuates arsenic trioxide‑induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress

  • Authors:
    • Woo Hyun Park
  • View Affiliations

  • Published online on: November 21, 2019     https://doi.org/10.3892/or.2019.7414
  • Pages: 358-367
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The thioredoxin (Trx) system is an important enzymatic complex involved in cellular redox homeostasis. Arsenic trioxide (ATO; As2O3) is known to trigger cell death in vascular smooth muscle cells (VSMCs) via oxidative stress. In the present study, the effects of changes in thioredoxin 1 (Trx1) and Trx reductase1 (TrxR1) on cell growth, death, reactive oxygen species (ROS), and glutathione (GSH) levels were evaluated in ATO‑treated human pulmonary artery smooth muscle cells (HPASMCs). ATO inhibited growth and induced cell death in the HPASMCs at 24 h. Overexpression of Trx1 and TrxR1 using adenoviruses attenuated cell growth inhibition caused by ATO and partially prevented cell death. ATO increased ROS levels including the mitochondrial superoxide anion (O2•-) at 5 min. Administration of adTrx1 or adTrxR1 reduced the increased mitochondrial O2•- level in these cells. HPASMCs treated with Trx1 or TrxR1 siRNA showed increases in ROS levels with or without treatment of ATO at 5 min. Although ATO transiently increased GSH levels at 5 min, Trx1 and TrxR1 siRNAs reduced the increased GSH levels in these cells. In addition, PX‑12 (a Trx1 inhibitor) and auranofin (a TrxR1 inhibitor) diminished the cellular metabolism in HPASMCs at 4 h, accompanied by an increase in ROS level and a decrease in GSH level. In conclusion, upregulation of Trx1 and TrxR1 somewhat decreased cell growth inhibition and death in ATO‑treated HPASMCs, which was accompanied by reduced oxidative stress.
View Figures
View References

Related Articles

Journal Cover

January-2020
Volume 43 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Park WH: Upregulation of thioredoxin and its reductase attenuates arsenic trioxide‑induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress. Oncol Rep 43: 358-367, 2020
APA
Park, W.H. (2020). Upregulation of thioredoxin and its reductase attenuates arsenic trioxide‑induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress. Oncology Reports, 43, 358-367. https://doi.org/10.3892/or.2019.7414
MLA
Park, W. H."Upregulation of thioredoxin and its reductase attenuates arsenic trioxide‑induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress". Oncology Reports 43.1 (2020): 358-367.
Chicago
Park, W. H."Upregulation of thioredoxin and its reductase attenuates arsenic trioxide‑induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress". Oncology Reports 43, no. 1 (2020): 358-367. https://doi.org/10.3892/or.2019.7414