PE-induced apoptosis in SMMC-7721 cells: Involvement of Erk and Stat signalling pathways

Emerging evidence indicates that the redistribution of phosphatidylethanolamine (PE) across the bilayer of the plasma membrane is an important molecular marker for apoptosis. However, the effect of PE on apoptosis and the underlying mechanism of PE remain unclear. In the current study, MTT and flow cytometric assays were used to examine the effects of PE on apoptosis in SMMC-7721 cells. The level of mitochondrial membrane potential (Delta Psi m) and the expression of Bax, Bcl-2, caspase-3, phospho-Erk and phospho-Stat1/2 in SMMC-7721 cells that were exposed to PE were also investigated. The results showed that PE inhibited proliferation, caused G0/G1 phase cell cycle arrest and induced apoptosis in SMMC-7721 cells in a dose-dependent manner. Rhodamine 123 staining showed that the treatment of SMMC-7721 cells with different concentrations of PE for 24 h significantly decreased the level of AIM and exerted dose-dependent effects. Using immunofluorescence and western blotting, we found that the expression of Bax was upregulated, whereas that of Bcl-2 was downregulated in PE-induced apoptotic cells. In addition, these events were accompanied by an increase in caspase-3 expression in a dose-dependent manner following PE treatment. PE-induced apoptosis was accompanied by a decrease in Erk phosphorylation and by the activation of Stat1/2 phosphorylation in SMMC-7721 cells. In conclusion, the results suggested that PE-induced apoptosis is involved in upregulating the Bax/Bcl-2 protein ratio and decreasing the Delta Psi m. Moreover, the results showed that the Erk and Stat1/2 signalling pathways may be involved in the process of PE-induced apoptosis.