Calcium Signaling of Lysophosphatidylethanolamine through LPA1 in Human SH-SY5Y Neuroblastoma Cells

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular $Ca^{2+}$ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with $LPA_1$ antagonists showed LPE induced intracellular $Ca^{2+}$ increases in an $LPA_1$ GPCR-dependent manner. Furthermore, LPE increased intracellular $Ca^{2+}$ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive $IP_3$ receptors, $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores, and subsequent $Ca^{2+}$ influx across plasma membranes, and LPA acted on $LPA_1$ and $LPA_2$ receptors to induce $Ca^{2+}$ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.