Details

Autor(en) / Beteiligte

• Kim, Kyeok
• Kim, Hyo-Lim
• Lee, Yun-Kyung
• Han, Mi-Jin
• Sacket, Santosh J
• Jo, Ji-Yeong
• Kim, Yu-Lee
• Im, Dong-Soon

Titel

Lysophosphatidylserine Induces Calcium Signaling through Ki16425/VPC32183-Sensitive GPCR in Bone Marrow-Derived Mast Cells and in C6 Glioma and Colon Cancer Cells

Ist Teil von

• Archives of pharmacal research, 2008, Vol.31 (3), p.310-317

Erscheinungsjahr

2008

Quelle

2022 ECC(Springer)

Beschreibungen/Notizen

• Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase $A_2$ activation. The effects of LPS on cellular activities and the identities of its target molecules, however, have not been fully elucidated. In this study, we observed that LPS stimulated intracellular calcium increased in mouse bone marrow-derived mast cells (BMMC), and rat C6 glioma and human HCT116 colon cancer cells and compared the LPS-induced $Ca^{2+}$ increases with the response by lysophosphatidic acid (LPA), a structurally related bioactive lysolipid. In order to test involvement of signaling molecules in the LPS-induced $Ca^{2+}$ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and $IP_3$ receptors, respectively. The increases due to LPS and LPA were inhibited by PTX, U-73122 and 2-APB, suggesting that both lipids stimulate calcium signaling via G proteins ($G_{i/o}$ types), PLC activation, and subsequent $IP_3$ production, although the sensitivity to pharmacological inhibitors varied from complete inhibition to partial inhibition depending on cell type and lysolipid. Furthermore, we observed that Ki16425 completely inhibited an LPS-induced $Ca^{2+}$ response in three cell types, but that the effect of VPC32183 varied from complete inhibition in BMMC and C6 glioma cells to partial inhibition in HCT116 cells. Therefore, we conclude that LPS increases $[Ca^{2+}]_i$ through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and $IP_3$ in mouse BMMC, rat C6, and human HCT116 cells.