Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation

involvement of LPA receptors.

Tae Joon Shin, Hyeon Joong Kim, Byeong Jae Kwon, Sun Hye Choi, Hyun Bum Kim, Sung Hee Hwang, Byung Hwan Lee, Sang Mok Lee, R. Suzanne Zukin, Ji Ho Park, Hyoung Chun Kim, Hyewhon Rhim, Joon Hee Lee, Seung Yeol Nah

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 Clchannels 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 (I ( NMDA )) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner. Gintonin-mediated I ( NMDA ) 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 I ( NMDA ) 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.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalMolecules and Cells
Volume34
Issue number6
StatePublished - 2012
Externally publishedYes

Fingerprint

Lysophosphatidic Acid Receptors
Panax
Long-Term Potentiation
N-Methylaspartate
Oocytes
Xenopus
gintonin
aspartic acid receptor
Lysophospholipids
Inositol 1,4,5-Trisphosphate Receptors
Complementary RNA
Protein Tyrosine Phosphatases
Patch-Clamp Techniques
Chelating Agents
GTP-Binding Proteins
Protein-Tyrosine Kinases
Protein Kinase C
Hippocampus
Electrodes

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Cell Biology

Cite this

Shin, T. J., Kim, H. J., Kwon, B. J., Choi, S. H., Kim, H. B., Hwang, S. H., ... Nah, S. Y. (2012). Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: involvement of LPA receptors. Molecules and Cells, 34(6), 563-572.

Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation : involvement of LPA receptors. / Shin, Tae Joon; Kim, Hyeon Joong; Kwon, Byeong Jae; Choi, Sun Hye; Kim, Hyun Bum; Hwang, Sung Hee; Lee, Byung Hwan; Lee, Sang Mok; Zukin, R. Suzanne; Park, Ji Ho; Kim, Hyoung Chun; Rhim, Hyewhon; Lee, Joon Hee; Nah, Seung Yeol.

In: Molecules and Cells, Vol. 34, No. 6, 2012, p. 563-572.

Research output: Contribution to journalArticle

Shin, TJ, Kim, HJ, Kwon, BJ, Choi, SH, Kim, HB, Hwang, SH, Lee, BH, Lee, SM, Zukin, RS, Park, JH, Kim, HC, Rhim, H, Lee, JH & Nah, SY 2012, 'Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: involvement of LPA receptors.', Molecules and Cells, vol. 34, no. 6, pp. 563-572.
Shin, Tae Joon ; Kim, Hyeon Joong ; Kwon, Byeong Jae ; Choi, Sun Hye ; Kim, Hyun Bum ; Hwang, Sung Hee ; Lee, Byung Hwan ; Lee, Sang Mok ; Zukin, R. Suzanne ; Park, Ji Ho ; Kim, Hyoung Chun ; Rhim, Hyewhon ; Lee, Joon Hee ; Nah, Seung Yeol. / Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation : involvement of LPA receptors. In: Molecules and Cells. 2012 ; Vol. 34, No. 6. pp. 563-572.
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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 Clchannels 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 (I ( NMDA )) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner. Gintonin-mediated I ( NMDA ) 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 I ( NMDA ) 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.",
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AU - Kwon, Byeong Jae

AU - Choi, Sun Hye

AU - Kim, Hyun Bum

AU - Hwang, Sung Hee

AU - Lee, Byung Hwan

AU - Lee, Sang Mok

AU - Zukin, R. Suzanne

AU - Park, Ji Ho

AU - Kim, Hyoung Chun

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N2 - 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 Clchannels 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 (I ( NMDA )) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner. Gintonin-mediated I ( NMDA ) 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 I ( NMDA ) 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.

AB - 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 Clchannels 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 (I ( NMDA )) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner. Gintonin-mediated I ( NMDA ) 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 I ( NMDA ) 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.

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