1. Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis
- Author
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Zhen-xia Qin, Ying-he Hu, and Hui-yan Zhu
- Subjects
Small interfering RNA ,chemistry.chemical_element ,Apoptosis ,Cell Cycle Proteins ,Calcium ,Biology ,Calcium in biology ,Receptors, G-Protein-Coupled ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,Pharmacology (medical) ,bcl-2-Associated X Protein ,Pharmacology ,Neurons ,Gene knockdown ,Amyloid beta-Peptides ,Caspase 3 ,Lysophosphatidylcholines ,General Medicine ,Molecular biology ,Peptide Fragments ,Lysophosphatidylcholine ,chemistry ,Gene Expression Regulation ,Cell culture ,lipids (amino acids, peptides, and proteins) ,Original Article ,Signal transduction ,Signal Transduction - Abstract
We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on Abeta(1-42)-induced SH-SY5Y cell apoptosis.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.Long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Abeta(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 Abeta(1-42)-induced elevation of intracellular calcium. Interestingly, Abeta(1-42) significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Abeta(1-42)-induced neurotoxicity.The effects of LPC on Abeta(1-42)-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.
- Published
- 2009