Gintonin Enhances Proliferation, Late Stage Differentiation, and Cell Survival From Endoplasmic Reticulum Stress of Oligodendrocyte Lineage Cells

被引:14
作者
Al Mijan, Mohammad [1 ,2 ]
Kim, Ji Young [3 ]
Moon, So-Young [1 ,2 ]
Choi, Sun-Hye [4 ,5 ]
Nah, Seung-Yeol [4 ,5 ]
Yang, Hyun-Jeong [1 ,2 ]
机构
[1] Univ Brain Educ, Dept Integrat Biosci, Cheonan, South Korea
[2] Korea Inst Brain Sci, Seoul, South Korea
[3] Yonsei Univ, Coll Med, Dept Anesthesiol & Pain Med, Seoul, South Korea
[4] Konkuk Univ, Coll Vet Med, Ginsentol Res Lab, Seoul, South Korea
[5] Konkuk Univ, Coll Vet Med, Dept Physiol, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
gintonin; oligodendrocyte; proliferation; differentiation; ER stress; cell protection; LYSOPHOSPHATIDIC ACID; GENE-EXPRESSION; DISORDERS; MIGRATION; LESIONS; BRAIN;
D O I
10.3389/fphar.2019.01211
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Although evidence on myelin diseases is steadily accumulating, effective preventive or therapeutic strategies against them have not been established so far. Ginseng is well known for its beneficial effects on health and diseases; however, detailed studies on ginseng's effects on myelin-producing oligodendrocytes have not been performed yet. In this study, we investigated the function of gintonin-an active component of ginseng-on the proliferation, differentiation, and survival of oligodendrocyte lineage cells. We performed real-time percutaneous coronary intervention, Western blot, and immunocytochemistry on primary oligodendrocyte precursor cell cultures and in vitro myelinating co-cultures. Our results show that gintonin stimulates oligodendrocyte precursor cell proliferation. Gintonin's effect was inhibited by Ki16425, an antagonist of lysophosphatidic acid 1/3 receptors. Interestingly, with regard to cell differentiation, gintonin facilitated late differentiation of oligodendrocyte development, but not early differentiation. Moreover, it showed protective effects on oligodendrocyte lineage cells against endoplasmic reticulum stress-induced cell death, potentially by modulating unfolded protein responses. Our results suggest that gintonin is a potential therapeutic candidate in the treatment of myelin diseases.
引用
收藏
页数:12
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共 27 条
[1]   A rat G protein-coupled receptor selectively expressed in myelin-forming cells [J].
Allard, J ;
Barrón, S ;
Diaz, J ;
Lubetzki, C ;
Zalc, B ;
Schwartz, JC ;
Sokoloff, P .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (03) :1045-1053
[2]   Oligodendrocyte Development and Plasticity [J].
Bergles, Dwight E. ;
Richardson, William D. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2016, 8 (02)
[3]   Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models [J].
Boyd, Amanda ;
Zhang, Hui ;
Williams, Anna .
ACTA NEUROPATHOLOGICA, 2013, 125 (06) :841-859
[4]   Oligodendrocytes: biology and pathology [J].
Bradl, Monika ;
Lassmann, Hans .
ACTA NEUROPATHOLOGICA, 2010, 119 (01) :37-53
[5]   A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function [J].
Cahoy, John D. ;
Emery, Ben ;
Kaushal, Amit ;
Foo, Lynette C. ;
Zamanian, Jennifer L. ;
Christopherson, Karen S. ;
Xing, Yi ;
Lubischer, Jane L. ;
Krieg, Paul A. ;
Krupenko, Sergey A. ;
Thompson, Wesley J. ;
Barres, Ben A. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (01) :264-278
[6]   NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions [J].
Chang, A ;
Nishiyama, A ;
Peterson, J ;
Prineas, J ;
Trapp, BD .
JOURNAL OF NEUROSCIENCE, 2000, 20 (17) :6404-6412
[7]   Multi-Target Protective Effects of Gintonin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Mediated Model of Parkinson's Disease via Lysophosphatidic Acid Receptors [J].
Choi, Jong Hee ;
Jang, Minhee ;
Oh, Seikwan ;
Nah, Seung-Yeol ;
Cho, Ik-Hyun .
FRONTIERS IN PHARMACOLOGY, 2018, 9
[8]   Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis [J].
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 .
MOLECULAR NEUROBIOLOGY, 2019, 56 (05) :3280-3294
[9]   Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia [J].
Clayton, Benjamin L. L. ;
Popko, Brian .
BRAIN RESEARCH, 2016, 1648 :594-602
[10]   Molecular Control of Oligodendrocyte Development [J].
Elbaz, Benayahu ;
Popko, Brian .
TRENDS IN NEUROSCIENCES, 2019, 42 (04) :263-277