Perfluorooctane sulfonate induces apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins in PC12 cells.

Abstract

Perfluorooctane sulfonate (PFOS), a kind of organic pollutant widely found in the environment and biota, could alter normal brain development and produce cognitive dysfunction. For the past years, the neurotoxic effects of PFOS have been shown. Recent studies have proven that PFOS can induce neuronal apoptosis and cause neurotoxicity, but the regulatory proteins referred to the process have not been clarified. In this study, PC12 cells were used to investigate the changes of the expression of apoptosis-related proteins, forkhead box O3 (FoxO3a) and pro-apoptotic Bcl-2 proteins. We detected that the levels of cleaved caspase-3 and cleaved PARP were up-regulated obviously in PFOS-treated PC12 cells by using Western blotting, and that the apoptotic rate of PC12 cells was increased significantly by using flow cytometry, verifying that PFOS could induce neuronal apoptosis. Western blot analysis and immunofluorescence revealed obvious up-regulation of the expression of FoxO3a and proapoptotic Bcl-2 proteins. In addition, knockdown of FoxO3a gene inhibited Bim expression and apoptosis. According to the data, we believe that FoxO3a may play a crucial role in PFOS-induced neurotoxicity.