The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH Oxidase-mediated Pathways

  • Cui, Yanji (Department of Physiology, Jeju National University School of Medicine) ;
  • Park, Jee-Yun (Department of Physiology, Jeju National University School of Medicine) ;
  • Wu, Jinji (Department of Physiology, Jeju National University School of Medicine) ;
  • Lee, Ji Hyung (Department of Physiology, Jeju National University School of Medicine) ;
  • Yang, Yoon-Sil (Department of Physiology, Jeju National University School of Medicine) ;
  • Kang, Moon-Seok (Department of Physiology, Jeju National University School of Medicine) ;
  • Jung, Sung-Cherl (Department of Physiology, Jeju National University School of Medicine) ;
  • Park, Joo Min (Department of Physiology, Jeju National University School of Medicine) ;
  • Yoo, Eun-Sook (Department of Pharmacology, Jeju National University School of Medicine) ;
  • Kim, Seong-Ho (BotaMedi Inc. 307 Jeju Bio-industry Center) ;
  • Ahn Jo, Sangmee (Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine and Department of Pharmacology, Dankook University) ;
  • Suk, Kyoungho (Department of Pharmacology, Kyungpook National University School of Medicine) ;
  • Eun, Su-Yong (Department of Physiology, Jeju National University School of Medicine)
  • Received : 2014.11.10
  • Accepted : 2015.02.23
  • Published : 2015.05.01
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Abstract

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

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References

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