Lysophosphatidylethanolamine increases intracellular Ca2+ through LPA1 in PC-12 neuronal cells
Introduction
Lysophosphatidic acid (LPA) is a representative lyso-type intercellular mediator that acts through G protein-coupled receptors (GPCRs; LPA1-6) [1]. Another lysolipid, lysophosphatidylethanolamine (LPE) has been detected in human serum at concentrations of several hundreds of ng/ml [2], [3]. However, its action has not been much studied. In SK-OV3 and OVCAR-3 ovarian cancer cells, the effect of LPE on intracellular Ca2+ ([Ca2+]i) was suggested to be mediated through GPCRs, but not through GPCRs for LPA [4]. On the other hand, in MDA-MB-231 cells, LPE-induced [Ca2+]i increases were observed to be mediated via the GPCRs of LPA1 and CD97 [5], [6]. These findings show increases in [Ca2+]i by LPE may be either dependent or independent of LPA1 in different cells.
In a previous study, several types of LPEs isolated from Grifola frondosa were found to induce neuronal differentiation and suppress serum-deprivation induced apoptosis via MAPK activation in PC12 neuronal cells [7]. However, the involvements of GPCRs in these processes and the action mechanisms involved have not been elucidated. Therefore, in the present study, we investigated the signaling of LPE in PC-12 in neuronal cells and the mechanism involved.
Section snippets
Materials
1-Oleoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (18:1 LPE), 1-stearoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (18:0 LPE), 1-octadecyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (ether-linked 18:0 LPE), 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (16:0 LPE), 1-myristoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (14:0 LPE), 1-oleoyl-2-hydroxy-sn-glycero-3-phosphate (sodium salt), and VPC32183 were purchased from Avanti Polar Lipids (Alabaster, AL, USA). Fura 2-AM, EGTA,
LPE increased [Ca2+]i in PC-12 neuronal cells
Previously, we observed LPE-induced increases of [Ca2+]i in MDA-MB-231 breast cancer cells and SK-OV3 ovarian cancer cells [4], [5]. In the present study, we treated cells with structurally different LPEs, that is oleoyl LPE (18:1 LPE), stearoyl LPE (18:0 LPE), octadecanyl LPE (ether-linked 18:0 LPE), palmitoyl LPE (16:0 LPE), and myristoyl LPE (14:0 LPE). As shown in Fig. 1-A and B, synthetic LPEs, such as, 18:1 LPE, 18:0 LPE, 18:0 ether-linked LPE, and 14:0 LPE, induced transient [Ca2+]i
Discussion
In the present study, LPE-induced [Ca2+]i increase was found to be mediated via LPA1 in PC-12 neuronal cells. Five results support this finding: 1) the heterologous desensitization exhibited by LPE- and LPA-induced [Ca2+]i increases, 2) the abrogation of LPE-induced response by the LPA1 and LPA 3 antagonists, Ki16425 and VPC32183, 3) the Gi/o-coupling character of LPA1 and the PTX-sensitivity of LPE-induced [Ca2+]i increase observed in PC-12 cells, 4) the complete inhibition of LPE-induced
Conflict of interest
None.
Acknowledgments
This research was supported by the Basic Science Research Program of the Korean National Research Foundation (NRF) funded by the Korean Ministry of Education, Science and Technology (NRF-2011-0021158) and by the Korean National Research Foundation funded by the Korean government (MSIP) (Grant no. 2009–0083538).
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