Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis.

AbstractAim:We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on Aβ_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 Aβ_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 Aβ_1–42-induced elevation of intracellular calcium. Interestingly, Aβ_1–42 significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Aβ_1–42-induced neurotoxicity.Conclusion:The effects of LPC on Aβ_1–42-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.Acta Pharmacologica Sinica (2009) 30: 388–395; doi: 10.1038/aps.2009.25 [ABSTRACT FROM AUTHOR]