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