Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway.
10.4196/kjpp.2019.23.2.121
- Author:
Yanji CUI
1
;
Khulan AMARSANAA
;
Ji Hyung LEE
;
Jong Kook RHIM
;
Jung Mi KWON
;
Seong Ho KIM
;
Joo Min PARK
;
Sung Cherl JUNG
;
Su Yong EUN
Author Information
1. Department of Physiology, Jeju National University School of Medicine, Jeju 63243, Korea. syeun@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Dieckol;
Glutamate toxicity;
Heme oxygenase-1;
Mitochondria;
Neurons;
Reactive oxygen species
- MeSH:
Adenine;
Brain;
Cell Death;
Cell Survival;
Cell-Free System;
Glutamic Acid*;
Heme Oxygenase-1;
Membrane Potential, Mitochondrial;
Mitochondria;
Neurodegenerative Diseases;
Neurons;
Reactive Oxygen Species*
- From:The Korean Journal of Physiology and Pharmacology
2019;23(2):121-130
- CountryRepublic of Korea
- Language:English
-
Abstract:
Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons (100 µM, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner (1–50 µM) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of Ca²⁺ and ROS, mitochondrial membrane potential (ΔΨ(m)) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.
