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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

  • Cui, Yanji (Department of Physiology, Jeju National University School of Medicine) ;
  • Amarsanaa, Khulan (Department of Physiology, Jeju National University School of Medicine) ;
  • Lee, Ji Hyung (Department of Physiology, Jeju National University School of Medicine) ;
  • Rhim, Jong-Kook (Department of Neurosurgery, Jeju National University School of Medicine) ;
  • Kwon, Jung Mi (Division of Hematology-Oncology, Department of Internal Medicine, Jeju National University School of Medicine) ;
  • Kim, Seong-Ho (BotaMedi Inc.) ;
  • Park, Joo Min (Center for Cognition and Sociality, Institute for Basic Science (IBS), KAIST) ;
  • Jung, Sung-Cherl (Department of Physiology, Jeju National University School of Medicine) ;
  • Eun, Su-Yong (Department of Physiology, Jeju National University School of Medicine)
  • Received : 2018.11.08
  • Accepted : 2019.01.16
  • Published : 2019.03.01

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 ($100{\mu}M$, 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 ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) 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.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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