Gintonin, a Ginseng-Derived Novel Ingredient, Evokes Long-Term Potentiation through N-methyl-D-aspartic Acid Receptor Activation: Involvement of LPA Receptors

Title
Gintonin, a Ginseng-Derived Novel Ingredient, Evokes Long-Term Potentiation through N-methyl-D-aspartic Acid Receptor Activation: Involvement of LPA Receptors
Authors
신태준김현중권병재최선혜김현범황성희이병환이상목R. Suzanne Zukin박지호김형춘임혜원이준희나승열
Keywords
ginseng; gintonin; LPA receptors; N-methyl-D-aspartic acid receptor; LTP
Issue Date
2012-12
Publisher
Molecules and cells
Citation
VOL 34, 563-572
Abstract
Ginseng has been shown to have memory-improving effects in human. However, little is known about the active components and the molecular mechanisms underlying its effects. Recently, we isolated novel lysophosphatidic acids (LPAs)-ginseng protein complex derived from ginseng, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity. Gintonin activated Ca2+-activated Cl- channels in Xenopus oocytes through the activation of endogenous LPA receptor. In the present study, we investigated whether the activation of LPA receptor by gintonin is coupled to the regulation of N-methyl-D-aspartic acid (NMDA) receptor channel activity in Xenopus oocytes expressing rat NMDA receptors. The NMDA receptor-mediated ion current (INMDA) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced INMDA in a concentration-dependent manner. Gintonin- mediated INMDA enhancement was blocked by Ki16425, an LPA1/3 receptor antagonist. Gintonin action was blocked by a PLC inhibitor, IP3 receptor antagonist, Ca2+ chelator, and a tyrosine kinase inhibitor. The site-directed mutation of Ser1308 of the NMDA receptor, which is phosphorylated by protein kinase C (PKC), to an Ala residue, or co-expression of receptor protein tyrosine phosphatase with the NMDA receptor attenuated gintonin action. Moreover, gintonin treatment elicited a transient elevation of [Ca2+]i in cultured hippocampal neurons and elevated longterm potentiation (LTP) in both concentration-dependent manners in rat hippocampal slices. Gintonin-mediated LTP induction was abolished by Ki16425. These results indicate that gintonin-mediated INMDA potentiation and LTP induction in the hippocampus via the activation of LPA receptor might be responsible for ginseng-mediated improvement of memory-related brain functions.
URI
http://pubs.kist.re.kr/handle/201004/46207
ISSN
10168478
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KIST Publication > Article
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