Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis

Aim: We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on A beta(1-42)-induced SH-SY5Y cell apoptosis. Methods: The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chip-based flow cytometric assay. The mRNA transcription of Bcl-2, Bax, and caspase-3 were detected by using reverse transcription and real-time quantitative PCR and the protein levels of Bax and caspase-3 were analyzed by Western blotting. The cytosolic calcium concentration of SH-SY5Y cells was tested by calcium influx assay. G2A expression in SH-SY5Y cells was silenced by small interfering RNA. Results: Long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of A beta(1-42). Furthermore, after LPC treatment, the Bax/Bcl-x(L) ratio and the expression levels, as well as the activity of caspase-3 were, elevated, whereas the expression level of TRAF1 was reduced. Because LPC was reported to be a specific ligand for the orphan G-protein coupled receptor, G2A, we investigated LPC-mediated changes in calcium levels in SH-SY5Y cells. Our results demonstrated that LPC can enhance the A beta(1-42)-induced elevation of intracellular calcium. Interestingly, A beta(1-42)-significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on A beta(1-42)-induced neurotoxicity. Conclusion: The effects of LPC on A beta(1-42)-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.