KMID : 0811720190230020121
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Korean Journal of Physiology & Pharmacology 2019 Volume.23 No. 2 p.121 ~ p.130
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Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway
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Cui Yanji
Amarsanaa Khulan Lee Ji-Hyung Rhim Jong-Kook Kwon Jung-Mi Kim Seong-Ho Park Joo-Min Jung Sung-Cherl Eun Su-Yong
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Abstract
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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 ¥ìM, 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 ¥ìM) 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 (¥Ä¥×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.
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KEYWORD
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Dieckol, Glutamate toxicity, Heme oxygenase-1, Mitochondria, Neurons, Reactive oxygen species
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