Choi, Sun-Hye Kim, Hyeon-Joong Cho, Hee-Jung Park, Sang-Deuk Lee, Na-Eun Hwang, Sung-Hee Cho, Ik-Hyun Hwang, Hongik Rhim, Hyewhon Kim, Hyoung-Chun Nah, Seung-Yeol 2024-01-19T20:03:41Z 2024-01-19T20:03:41Z 2021-09-02 2019-05 0893-7648 https://pubs.kist.re.kr/handle/201004/120046 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-G(q/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. English SPRINGER Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis Article 10.1007/s12035-018-1308-1 1 Molecular Neurobiology, v.56, no.5, pp.3280 - 3294 Molecular Neurobiology 56 5 3280 3294 N scie scopus 000468535100015 2-s2.0-85051786981 Neurosciences Neurosciences & Neurology Article VASOACTIVE-INTESTINAL-PEPTIDE FUNCTIONAL IMPACT GLUTAMATE UPTAKE RAT ASTROCYTES GLUCOSE BRAIN METABOLISM MECHANISMS EXPRESSION HEALTH Gintonin LPA receptor Astrocytes Glycogenolysis Hypoxia Cell viability