Pb(NO3)2induces cell apoptosis through triggering of reactive oxygen species accumulation and disruption of mitochondrial function viaSIRT3/SOD2pathways

Abstract

AbstractLead (Pb) is nonbiodegradable and toxic to the lungs. To investigate the potential mechanisms of Pb‐induced reactive oxygen species (ROS) accumulation and cell death in the lungs, human non‐small lung carcinoma H460 cells were stimulated with Pb(NO3)2in this study. The results showed that Pb(NO3)2stimulation increased cell death by inducing cell apoptosis which showed a reduced Bcl‐2 expression and an enhanced caspase 3 activation. Pb(NO3)2also caused the production of H2O2in H460 cells that triggering the buildup of ROS and mitochondrial membrane potential loss. We found that Pb(NO3)2modulates oxidoreductive activity through reduced the glutathione‐disulfide reductase and glutathione levels in Pb(NO3)2‐exposed H460 cells. Furthermore, the superoxide dismutase (SOD) upstream molecule sirtuin 3 (SIRT3) was increased with Pb(NO3)2dose. Collectively, these results demonstrate that Pb(NO3)2promotes lung cell death through SIRT3/SOD‐mediated ROS accumulation and mitochondrial dysfunction.