Upregulation of thioredoxin and its reductase attenuates arsenic trioxide-induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress
Upregulation of thioredoxin and its reductase attenuates arsenic trioxide-induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress
复制标题
上调硫氧还蛋白及其还原酶通过减轻氧化应激减轻三氧化二砷诱导的人肺动脉平滑肌细胞生长抑制
DOI：
10.3892/or.2019.7414
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发表时间：
2020-01-01
期刊：
影响因子：
4.2
通讯作者：
Park, Woo Hyun
中科院分区：
文献类型：
--
作者：
Park, Woo Hyun
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 (O-2(center dot-)) at 5 min. Administration of adTrx1 or adTrxR1 reduced the increased mitochondrial O-2(center dot-) 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.
