Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules

Jong-Hoon Kim¹  Hyewhon Rhim²  Byung-Joo Kim³  Seung-Yeol Nah⁴  Han-Sung Cho⁴  Ra-Mi Lee⁴  Sun-Hye Choi⁴  Yeon-Jin Cho⁴  Hyoung-Chun Kim⁵ 

[1] Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Baekje-daero 567, Jeonju 28644, Korea;Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Korea;Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Korea;Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea;Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Korea;

关键词: ginseng;    gintonin;    hippocampal cell line;    oxidative stress;    BDNF/TrkB/Akt;    neuroprotection;   

DOI  :  10.3390/molecules26144138

来源: DOAJ

【 摘 要 】

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca²⁺]_i transients in HT22 cells. Gintonin-mediated [Ca²⁺]_i transients through the LPA1 receptor-PLC-IP₃ signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

【 授权许可】

Unknown