Mechanism of apoptosis and its pathway induced by perfluorooctane sulfonate(PFOS) in murine glial cells

Objective To evaluate the apoptosis of murine microghia N9 cells related to mitochondrial function after PFOS exposure.Methods The N9 cells were exposed to PFOS at concentrations 5,10,50,100,and 200 μmol/L for 24 and 48 hours,respectively,and the controls were exposed to 0.5% dimethyl sulfoxide(DMSO).The apoptotic celluar ratio was detected by flow cytometry 24 hours after the exposure.Mitochondrial membrane potential(MMP) was measured by Rhodamine 123 and the expressions of p53,Bax,Bcl-2,caspase-3,and caspase-9 mRNA were detected by real-time (RT)-PCR after the exposure for 24 and 48 hours.β-actin was used as the internal reference gene.Results Compared with the apoptotic ratio(2.24%) of the control group,statistically significant increases in apoptotic celluar ratio were observed in 50,100,and 200 μmol/L PFOS exposure groups(20.81%,33.26%,and 48.72%).The dissipation of MMP was observed with punctate perinuclear fluorescence after 200 μmol/L PFOS exposure.But no dose-dependent up-regulation of p53,Bax,caspase-3,and caspase-9 mRNAs,and down-regulation of Bcl-2 mRNA were involved after PFOS exposure.Conclusion The results suggest that cell apoptosis induced by PFOS is mainly mediated by mitochrondrial pathway,in which PFOS could disturb homeostasis of microglial cells,impact mitochondria,and affect gene expression of apoptotic regulators.