title: Lysophosphatidylserine induces calcium signaling through Ki16425/VPC32183-sensitive GPCR in bone marrow-derived mast cells and in C6 glioma and colon cancer cells.
abstract: Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase A2 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 Ca2+ 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 Ca2+ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and IP3 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 (Gi/o types), PLC activation, and subsequent IP3 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 Ca2+ 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 [Ca2+]i through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and IP3 in mouse BMMC, rat C6, and human HCT116 cells.
authors.affiliation: Laboratory of Pharmacology, College of Pharmacy (BK21 Project), Pusan National University, San 30, Jang-Jun-dong, Geum-Jung-gu, Busan 609-735, Korea.
authors.forename: Kyeok
authors.initials: K
authors.lastname: Kim
authors.forename: Hyo-Lim
authors.initials: HL
authors.lastname: Kim
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Mijin
authors.initials: M
authors.lastname: Han
authors.forename: Santosh J
authors.initials: SJ
authors.lastname: Sacket
authors.forename: Ji-Yeong
authors.initials: JY
authors.lastname: Jo
authors.forename: Yu-Lee
authors.initials: YL
authors.lastname: Kim
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D004791:Enzyme Inhibitors; D004963:Estrenes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007555:Isoxazoles; D008246:Lysophospholipids; D010755:Organophosphates; D011422:Propionates; D011725:Pyridines; D011760:Pyrrolidinones; D049368:Receptors, Lysophosphatidic Acid; C529824:VPC32183; C025059:lysophosphatidylserine; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D010738:Type C Phospholipases; C032881:lysophosphatidic acid