Rahman, Md Ataur Hwang, Hongik Nah, Seung-Yeol Rhim, Hyewhon 2024-01-19T18:31:13Z 2024-01-19T18:31:13Z 2022-01-10 2020-01 1226-8453 https://pubs.kist.re.kr/handle/201004/119122 Background: Gintonin (GT), a novel ginseng-derived exogenous ligand of lysophosphatidic acid (LPA) receptors, has been shown to induce cell proliferation and migration in the hippocampus, regulate calcium-dependent ion channels in the astrocytes, and reduce beta-amyloid plaque in the brain. However, whether GT influences autophagy in cortical astrocytes is not yet investigated. Methods: We examined the effect of GT on autophagy in primary cortical astrocytes using immunoblot and immunocytochemistry assays. Suppression of specific proteins was performed via siRNA. LC3 puncta was determined using confocal microscopy. Results: GT strongly upregulated autophagy marker LC3 by a concentration- as well as time-dependent manner via G protein-coupled LPA receptors. GT-induced autophagy was further confirmed by the formation of LC3 puncta. Interestingly, on pretreatment with an mammalian target of rapamycin (mTOR) inhibitor, rapamycin, GT further enhanced LC3-II and LC3 puncta expression. However, GT-induced autophagy was significantly attenuated by inhibition of autophagy by 3-methyladenine and knockdown Beclin-1, Atg5, and Atg7 gene expression. Importantly, when pretreated with a lysosomotropic agent, E-64d/peps A or bafilomycin A1, GT significantly increased the levels of LC3-II along with the formation of LC3 puncta. In addition, GT treatment enhanced autophagic flux, which led to an increase in lysosome-associated membrane protein 1 and degradation of ubiquitinated p62/SQSTM1. Conclusion: GT induces autophagy via mTOR-mediated pathway and elevates autophagic flux. This study demonstrates that GT can be used as an autophagy-inducing agent in cortical astrocytes. (C) 2018 The Korean Society of Ginseng. Publishing services by Elsevier B.V. English 고려인삼학회 Gintonin stimulates autophagic flux in primary cortical astrocytes Article 10.1016/j.jgr.2018.08.004 1 Journal of Ginseng Research, v.44, no.1, pp.67 - 78 Journal of Ginseng Research 44 1 67 78 Y scie scopus kci ART002550358 000505047900009 2-s2.0-85053892264 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article ACTIVATED PROTEIN-KINASE ACID RECEPTOR ACTIVATION CELL-DEATH GINSENG PATHWAYS MOUSE IMPAIRMENT NEURODEGENERATION PATHOGENESIS INVOLVEMENT Autophagic flux Autophagy-related genes Gintonin LC3 puncta p62/SQSTM1