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

Mohammad Al Mijan; Ji Young Kim; So-Young Moon; Sun-Hye Choi; Seung-Yeol Nah; Hyun-Jeong Yang

doi:10.3389/fphar.2019.01211

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

Front Pharmacol. 2019 Oct 8:10:1211. doi: 10.3389/fphar.2019.01211. eCollection 2019.

Authors

Mohammad Al Mijan^{1

2}, Ji Young Kim³, So-Young Moon^{1

2}, Sun-Hye Choi⁴, Seung-Yeol Nah⁴, Hyun-Jeong Yang^{1

2}

Affiliations

¹ Department of Integrative Biosciences, University of Brain Education, Cheonan, South Korea.
² Korea Institute of Brain Science, Seoul, South Korea.
³ Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, South Korea.
⁴ Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea.

Abstract

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.

Keywords: ER stress; cell protection; differentiation; gintonin; oligodendrocyte; proliferation.