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Molecular Neurobiology

, Volume 56, Issue 5, pp 3280–3294 | Cite as

Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis

  • Sun-Hye Choi
  • Hyeon-Joong Kim
  • Hee-Jung Cho
  • Sang-Deuk Park
  • Na-Eun Lee
  • Sung-Hee Hwang
  • Ik-Hyun Cho
  • Hongik Hwang
  • Hyewhon Rhim
  • Hyoung-Chun Kim
  • Seung-Yeol NahEmail author
Article

Abstract

Astrocytes are a unique brain cell-storing glycogen and express lysophosphatidic acid (LPA) receptors. Gintonin is a ginseng-derived exogenous G protein-coupled LPA receptor ligand. Accumulating evidence shows that astrocytes serve as an energy supplier to neurons through astrocytic glycogenolysis under physiological and pathophysiological conditions. However, little is known about the relationships between LPA receptors and astrocytic glycogenolysis or about the roles of LPA receptors in hypoxia and re-oxygenation stresses. In the present study, we examined the functions of gintonin-mediated astrocytic glycogenolysis in adenosine triphosphate (ATP) production, glutamate uptake, and cell viability under normoxic, hypoxic, and re-oxygenation conditions. The application of gintonin or LPA to astrocytes induced glycogenolysis in concentration- and time-dependent manners. The stimulation of gintonin-mediated astrocytic glycogenolysis was achieved through the LPA receptor-Gαq/11 protein-phospholipase C-inositol 1,4,5-trisphosphate receptor-intracellular calcium ([Ca2+]i) transient pathway. Gintonin treatment to astrocytes increased the phosphorylation of brain phosphorylase kinase, with sensitive manner to K252a, an inhibitor of phosphorylase kinase. Gintonin-mediated astrocytic glycogenolysis was blocked by isofagomine, a glycogen phosphorylase inhibitor. Gintonin additionally increased astrocytic glycogenolysis under hypoxic and re-oxygenation conditions. Moreover, gintonin increased ATP production, glutamate uptake, and cell viability under the hypoxic and re-oxygenation conditions. Collectively, we found that the gintonin-mediated [Ca2+]i transients regulated by LPA receptors were coupled to astrocytic glycogenolysis and that stimulation of gintonin-mediated astrocytic glycogenolysis was coupled to ATP production and glutamate uptake under hypoxic and re-oxygenation conditions, ultimately protecting astrocytes. Hence, the gintonin-mediated astrocytic energy that is modulated via LPA receptors helps to protect astrocytes under hypoxia and re-oxygenation stresses.

Keywords

Gintonin LPA receptor Astrocytes Glycogenolysis Hypoxia Cell viability 

Notes

Acknowledgments

This study was supported by a grant from the Basic Science Research Program from the Brain Research Program (NRF-2017R1D1A1A09000520) through the NRF of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2016M3C7A1913845) to S-Y. Nah.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sun-Hye Choi
    • 1
  • Hyeon-Joong Kim
    • 1
  • Hee-Jung Cho
    • 1
  • Sang-Deuk Park
    • 1
  • Na-Eun Lee
    • 1
  • Sung-Hee Hwang
    • 2
  • Ik-Hyun Cho
    • 3
  • Hongik Hwang
    • 4
  • Hyewhon Rhim
    • 4
  • Hyoung-Chun Kim
    • 5
  • Seung-Yeol Nah
    • 1
    Email author
  1. 1.Ginsentology Research Laboratory and Department of Physiology, College of Veterinary MedicineKonkuk UniversitySeoulSouth Korea
  2. 2.Department of Pharmaceutical Engineering, College of Health SciencesSangji UniversityWonjuSouth Korea
  3. 3.Department of Convergence Medical Science, College of Korean MedicineKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Center for NeuroscienceKorea Institute of Science and TechnologySeoulSouth Korea
  5. 5.Neuropsychopharmacology and Toxicology program, College of PharmacyKangwon National UniversityChunchonSouth Korea

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