Open AccessThioredoxin mitigates H 2 O 2 ‐induced inhibition of myogenic differentiation of rat bone marrow mesenchymal stem cells by enhancing AKT activation
Author(s) -
Liu Meiling,
Li Xianglu,
Zhou Changlin,
Wang Manfeng,
Wang Hongzhi,
Ding Haifeng,
Cheng Luyang,
Gan Lu,
Wu Xiaowei,
Du Zhimin
Publication year - 2020
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12835
Subject(s) - wortmannin , mesenchymal stem cell , microbiology and biotechnology , cellular differentiation , chemistry , protein kinase b , biology , signal transduction , biochemistry , gene
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 (H 2 O 2 ) on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µ m ) of H 2 O 2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase and glutathione peroxidase levels, and an increase in reactive oxygen species and malondialdehyde levels, which was accompanied by reductions in protein kinase B activation and forkhead Box O1, myogenic differentiation 1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human Trx significantly mitigated the effects of H 2 O 2 on the myogenic differentiation of BMSCs, and this was abrogated by cotreatment with wortmannin [a specific phosphatidylinositol 3‐kinase inhibitor]. In summary, our results suggest that treatment with recombinant human Trx mitigates H 2 O 2 ‐induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing phosphatidylinositol 3‐kinase/protein kinase B/forkhead Box O1 signaling.