3 years ago

Thioredoxin mitigates H2O2‐induced inhibition of myogenic differentiation of rat bone marrow mesenchymal stem cells by enhancing AKT activation

Meiling Liu, Xianglu Li, Changlin Zhou, Manfeng Wang, Hongzhi Wang, Haifeng Ding, Luyang Cheng, Lu Gan, Xiaowei Wu, Zhimin Du

Thioredoxin (Trx) is a hydrogen acceptor of ribonucleotide reductase, and a regulator of some enzymes and receptors. It has been previously shown that significantly elevated levels of Trx expression are associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but it is not clear how Trx regulates the effects of hydrogen peroxide on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µmol/L) of H2O2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase (SOD) and glutathione peroxidase (GSH‐PX) levels, and an increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, which was accompanied by reductions in AKT activation and FoxO1, MyoD1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human (rh)Trx significantly mitigated the effects of H2O2 on the myogenic differentiation of BMSCs, and this was abrogated by co‐treatment with wortmannin (a specific PI3K inhibitor). In summary, our results suggest that treatment with rhTrx mitigates H2O2‐induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing PI3K/AKT/FoxO1 signaling.

Open access
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