Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis

• Published in: Acta pharmacologica Sinica Vol. 30; no. 4; pp. 388 - 395
• Main Authors: Qin, Zhen-xia, Zhu, Hui-yan, Hu, Ying-he
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2009; Nature Publishing Group
• Subjects: Amyloid beta-Peptides - toxicity; Apoptosis - drug effects; bcl-2-Associated X Protein - analysis; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; caspase; Caspase 3 - analysis; Cell Cycle Proteins - physiology; Cell Line, Tumor; Gene Expression Regulation; Humans; Immunology; Internal Medicine; Lysophosphatidylcholines - pharmacology; Medical Microbiology; Neurons - drug effects; Original; original-article; Peptide Fragments - toxicity; Pharmacology/Toxicology; Receptors, G-Protein-Coupled - physiology; Signal Transduction; SY5Y细胞; Vaccine; 孤儿G蛋白偶联受体; 流式细胞仪检测; 淀粉样; 溶血磷脂酰胆碱; 神经细胞凋亡; 蛋白诱导; lysophosphatidylcholine; amyloid beta (1–42) peptide; neuronal apoptosis
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2009.25

Aim： We have investigated the effects of lysophosphatidylcholine （LPC）, a product of lipid peroxidation, on Aβ1-42-induced SH-SY5Y cell apoptosis. Methods： The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chipased 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 Aβ1-42, Furthermore, after LPC treatment, the Bax/Bcl-XL 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 Aβ1-42-induced elevation of intracellular calcium. Interestingly, Aβ1-42 significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Aβ1-42induced neurotoxicity. Conclusion： The effects of LPC on Aβ1-42-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.