
Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway
- Yanji Cui Khulan Amarsanaa Ji Hyung Lee Jong-Kook Rhim Jung Mi Kwon Seong-Ho Kim Joo Min Park Sung-C
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제23권 제2호
- 등재여부 : KCI등재
- 2019.03
- 121 - 130 (10 pages)
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 M, 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 M) 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 (Δ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 factorlike 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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