Reactive oxygen species mediate A beta(25-35)-induced activation of BV-2 microglia

Neuroreport. 2001 May 25;12(7):1449-52. doi: 10.1097/00001756-200105250-00030.

Abstract

Microglial activation induced by beta-amyloid (A beta) is an important cellular response in the pathogenesis of Alzheimer's disease (AD). In this study, we show that reactive oxygen species (ROS) play a role as signaling molecules for the activation of NF-kappaB and induction of IL-1beta mRNA expression in A beta(25-35)-treated murine microglia BV-2 cells. ROS scavengers such catalase and superoxide dismutase (SOD) mimetics obviously reduced activation of NF-kappaB and the elevated level of IL-1beta transcripts induced by A beta(25-35). In addition, the A beta(25-35)-induced NF-kappaB activation and IL-1beta expression were suppressed by blockers of the ROS generating enzymes such as NADPH oxidase, cyclooxygenase, and lipoxygenase. These data suggest that ROS mediate A beta-induced microglial activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Line, Transformed / drug effects
  • Cell Line, Transformed / metabolism
  • Cell Line, Transformed / pathology
  • Enzyme Inhibitors / pharmacology
  • Free Radical Scavengers / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Gliosis / chemically induced
  • Gliosis / metabolism
  • Gliosis / physiopathology
  • Interleukin-1 / genetics*
  • Lipoxygenase / drug effects
  • Lipoxygenase / metabolism
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • NADPH Oxidases / drug effects
  • NADPH Oxidases / metabolism
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / physiology

Substances

  • Amyloid beta-Peptides
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Interleukin-1
  • NF-kappa B
  • Peptide Fragments
  • RNA, Messenger
  • Reactive Oxygen Species
  • amyloid beta-protein (25-35)
  • Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • NADPH Oxidases