title: Vitamin K2 suppresses rotenone-induced microglial activation in vitro.
abstract: OBJECTIVE
  Increasing evidence has shown that environmental factors such as rotenone and paraquat induce neuroinflammation, which contributes to the pathogenesis of Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying the repression by menaquinone-4 (MK-4), a subtype of vitamin K2, of rotenone-induced microglial activation in vitro.
  
  
  METHODS
  A microglial cell line (BV2) was exposed to rotenone (1 μmol/L) with or without MK-4 treatment. The levels of TNF-α or IL-1β in 100 μL of cultured media of BV2 cells were measured using ELISA kits. BV2 cells treated with rotenone with or without MK4 were subjected to mitochondrial membrane potential, ROS production, immunofluorescence or immunoblot assays. The neuroblastoma SH-SY5Y cells were treated with conditioned media (CM) of BV2 cells that were exposed to rotenone with or without MK-4 treatment, and the cell viability was assessed using MTT assay.
  
  
  RESULTS
  In rotenone-treated BV2 cells, MK-4 (0.5-20 μmol/L) dose-dependently suppressed the upregulation in the expression of iNOS and COX-2 in the cells, as well as the production of TNF-α and IL-1β in the cultured media. MK-4 (5-20 μmol/L) significantly inhibited rotenone-induced nuclear translocation of NF-κB in BV2 cells. MK-4 (5-20 μmol/L) significantly inhibited rotenone-induced p38 activation, ROS production, and caspase-1 activation in BV2 cells. MK-4 (5-20 μmol/L) also restored the mitochondrial membrane potential that had been damaged by rotenone. Exposure to CM from rotenone-treated BV2 cells markedly decreased the viability of SH-SY5Y cells. However, this rotenone-activated microglia-mediated death of SH-SY5Y cells was significantly attenuated when the BV2 cells were co-treated with MK-4 (5-20 μmol/L).
  
  
  CONCLUSIONS
  Vitamin K2 can directly suppress rotenone-induced activation of microglial BV2 cells in vitro by repressing ROS production and p38 activation.
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.|Department of Pharmacy, Suzhou Hospital Affiliated with Nanjing Medical University, Suzhou 215002, China.
authors: Yan-Xia
authors: YX
authors: Yu
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
authors: Yi-Pei
authors: YP
authors: Li
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
authors: Feng
authors: F
authors: Gao
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
authors: Qing-Song
authors: QS
authors: Hu
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
authors: Yan
authors: Y
authors: Zhang
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
authors: Dong
authors: D
authors: Chen
authors: Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.|The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215021, China.
authors: Guang-Hui
authors: GH
authors: Wang
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D053583:Interleukin-1beta / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004785:Environmental Pollutants; D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; D024482:Vitamin K 2; C030814:menatetrenone