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KMID : 0578320120330020151
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Molecules and Cells
2012 Volume.33 No. 2 p.151 ~ p.162
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Gintonin, Newly Identified Compounds from Ginseng, Is Novel Lysophosphatidic Acids-Protein Complexes and Activates G Protein-Coupled Lysophosphatidic Acid Receptors with High Affinity
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Hwang Sung-Hee
Shin Tae-Joon
Choi Sun-Hye
Cho Hee-Jung
Lee Byung-Hwan
Pyo Mi-Kyung
Lee Jun-Ho
Kang Ji-Yeon
Kim Hyeon-Joong
Park Chan-Woo
Shin Ho-Chul
Nah Seung-Yeol
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Abstract
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Recently, we isolated a subset of glycolipoproteins from Panax ginseng, that we designated gintonin, and demon-strated that it induced [Ca2+]i transients in cells via G-protein-coupled receptor (GPCR) signaling pathway(s). However, active components responsible for Ca2+ mobili-zation and the corresponding receptor(s) were unknown. Active component(s) for [Ca2+]i transients of gintonin were analyzed by liquid chromatography-electrospray ioniza-tion-tandem mass spectrometry and ion-mobility mass spectrometry, respectively. The corresponding receptor(s) were investigated through gene expression assays. We found that gintonin contains LPA C18:2 and other LPAs. Proteomic analysis showed that ginseng major latex-like protein and ribonuclease-like storage proteins are protein components of gintonin. Gintonin induced [Ca2+]i tran-sients in B103 rat neuroblastoma cells transfected with human LPA receptors with high affinity in order of LPA2 > LPA5 > LPA1 > LPA3 > LPA4. The LPA1/LPA3 receptor antagonist Ki16425 blocked gintonin action in cells ex-pressing LPA1 or LPA3. Mutations of binding sites in the LPA3 receptor attenuated gintonin action. Gintonin acted via pertussis toxin (PTX)-sensitive and -insensitive G pro-tein-phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP3)- Ca2+ pathways. However, gintonin had no effects on other receptors examined. In human umbilical vein endothelial cells (HUVECs) gintonin stimulated cell proliferation and migration. Gintonin stimulated ERK1/2 phosphorylation. PTX blocked gintonin-mediated migration and ERK1/2 phosphorylation. In PC12 cells gintonin induced morpho-logical changes, which were blocked by Rho kinase inhibi-tor Y-27632. Gintonin contains GPCR ligand LPAs in com-plexes with ginseng proteins and could be useful in the development of drugs targeting LPA receptors.
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KEYWORD
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ginseng, gintonin, LPA-protein complexes, LPA receptors
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