Pb(NO 3 ) 2 induces cell apoptosis through triggering of reactive oxygen species accumulation and disruption of mitochondrial function via SIRT3/SOD2 pathways.

Lead (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(NO 3 ) 2 in this study. The results showed that Pb(NO 3 ) 2 stimulation increased cell death by inducing cell apoptosis which showed a reduced Bcl-2 expression and an enhanced caspase 3 activation. Pb(NO 3 ) 2 also caused the production of H 2 O 2 in H460 cells that triggering the buildup of ROS and mitochondrial membrane potential loss. We found that Pb(NO 3 ) 2 modulates oxidoreductive activity through reduced the glutathione-disulfide reductase and glutathione levels in Pb(NO 3 ) 2 -exposed H460 cells. Furthermore, the superoxide dismutase (SOD) upstream molecule sirtuin 3 (SIRT3) was increased with Pb(NO 3 ) 2 dose. Collectively, these results demonstrate that Pb(NO 3 ) 2 promotes lung cell death through SIRT3/SOD-mediated ROS accumulation and mitochondrial dysfunction.