Thioredoxin-1 Protects Bone Marrow-Derived Mesenchymal Stromal Cells from Hyperoxia-Induced Injury In Vitro

Figure 8

A schematic model of the regulation of the ASK1/P38 signal pathway by Trx-1. (a) The Trx-1 system contains NADPH, TrxR-1, and Trx-1. The oxidized Trx-1 (inactive form) is transformed to the active and reduced form of Trx-1 by receiving electrons from NADPH coenzyme in the presence of TrxR-1. Prxs reduce H₂O₂ to H₂O using electrons from the active Trx-1. The active Trx-1 also regulates redox signals by reducing many other target proteins with disulfide bonds. ASK1 constantly forms an inactive complex with reduced Trx-1 under normoxic conditions. (b) Exposure of BMSCs to hyperoxia leads to elevated ROS and H₂O₂ production, which leads to oxidative stress. However, oxidized Trx-1 is dissociated from ASK1 in response to oxidative stress and subsequent activation of ASK1. Activated ASK1 in turn activates the p38 pathway and induces various cellular responses, including cell apoptosis and differentiation inhibition. Trx-1 overexpression promoted BMSC survival under hyperoxic conditions through elevation of antioxidant activities, reduction of ROS and H₂O₂ generation, and subsequent inhibition of the ASK1/P38 signaling pathway.