title: Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH Oxidase-mediated Pathways.
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 µg/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.
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Yanji
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Jee-Yun
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Jinji
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Yoon-Sil
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Moon-Seok
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Sung-Cherl
authors.initials: SC
authors.lastname: Jung
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Joo Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
authors.affiliation: BotaMedi Inc. 307 Jeju Bio-industry Center, Jeju 690-121, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine and Department of Pharmacology, Dankook University, Cheonan 330-951, Korea.
authors.forename: Sangmee
authors.initials: S
authors.lastname: Ahn Jo
authors.affiliation: Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-842, Korea.
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.affiliation: Department of Physiology, Jeju National University School of Medicine, Jeju 690-756, Korea.
authors.forename: Su-Yong
authors.initials: SY
authors.lastname: Eun
keywords: Akt; Dieckol; Microglia; Neuron-microglia co-culture; gp91phox