Figure 9.

Schemes of the mechanism of the 1-NP-induced apoptosis and cytotoxicity in RAW264.7 cells. After RAW264.7 macrophages were incubated with 1-NP, it caused downregulation of cell viability via upregulation of apoptosis. 1-NP induced apoptosis by inducing AIF nuclear translocation, which was caused by mitochondrial dysfunction. Mitochondrial dysfunction induced by 1-NP occurred due to changes in the expression of BCL-2 family proteins, including downregulation of Bcl-2 and Bcl-xL and upregulation of Bad, Bax, Bid, and tBid. 1-NP induced ROS generation by mitochondrial dysfunction and reducing AOE activity. Additionally, 1-NP treatment led to the activation of the AMPK/Nrf-2/HO-1 pathway due to high levels of oxidative stress. These findings suggested that downregulation of cell viability induced by 1-NP via upregulation of apoptosis was due to mitochondrial dysfunction, AIF nuclear translocation, ROS generation, AOE activity reduction, and AMPK/Nrf-2/HO-1 pathway activation.