N-acetylcysteine attenuates PM-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cells.
Sci Total Environ. 2019 Feb 20 ;666:713-720. Epub 2019 Feb 20. PMID: 30818202
While the effects of fine particulate matter (PM) on embryonic toxicity are widely accepted, its exact mechanisms have not yet been fully elucidated, which partially attribute to lack of ideal research model. Embryonic stem cells (ESCs) have the capacity to differentiate into all cell types of three germ layers. Thus, they are ideal resources for the reproductive toxicity assessment in vitro. In the present study, we investigated the effects of PMexposure on the oxidative stress and apoptosis of human ESCs (hESCs) and its possible mechanism. Our results showed that strong cytotoxicity high reactive oxygen species (ROS) level and fragmentation of nuclei were observed in the PM-treated hESCs. Meanwhile, up-regulation of apoptosis as well as down-regulation of Nrf2 signaling pathway were also observed after PMtreatment. However, we did not detect significant expression change or phosphorylation of Akt and Erk in PM-treated hESCs. Interestingly, scavenging of PM-induced ROS by N-acetylcysteine (NAC) could block cell apoptosis and rescue the activity of Nrf2 signaling pathway. In conclusion, we demonstrate that PMis toxic to hESCs by inhibition of ROS-mediated Nrf2 pathway activity. Our findings suggest activation of Nrf2 pathway will help develop new strategies for the prevention and treatment of PM-associated disease.