Suppression of inducible nitric oxide synthase and cyclooxygenase-2 by cell-permeable superoxide dismutase in lipopolysaccharide-stimulated BV-2 microglial cells

Mol Cells. 2010 Mar;29(3):245-50. doi: 10.1007/s10059-010-0031-1. Epub 2010 Jan 21.


Oxidative stress plays a pivotal role in uncontrolled neuro-inflammation leading to many neurological diseases including Alzheimer's. One of the major antioxidant enzymes known to prevent deleterious effects due to oxidative stress is Cu,Zn-superoxide dismutase (SOD). In this study, we examined the regulatory function of SOD on the LPS-induced signaling pathways leading to NF-kappaB activation, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in BV-2 cells using cell-permeable SOD. Treatment of BV-2 cells with cell-permeable SOD led to a decrease in LPS-induced reactive oxygen species (ROS) generation and significantly inhibited protein and mRNA levels of iNOS and COX-2 upregulated by LPS. Production of NO and PGE2 in LPS stimulated BV-2 cells was significantly abrogated by pretreatment with a cell-permeable SOD fusion protein. Furthermore, cell-permeable SOD inhibited LPS-induced NF-kappaB DNA-binding activity and activation of MAP kinases including ERK, JNK, and p38 in BV-2 cells. These data indicate that SOD has a regulatory function for LPS-induced NF-kappaB activation leading to expression of iNOS and COX-2 in BV-2 cells and suggest that cell-permeable SOD is a feasible therapeutic agent for regulation of ROS-related neurological diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line / drug effects
  • Cell Line / enzymology
  • Cell Membrane Permeability
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Dinoprostone / biosynthesis
  • Down-Regulation / drug effects
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects
  • HIV-1 / genetics
  • Humans
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Microglia / drug effects
  • Microglia / enzymology*
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Nitric Oxide Synthase Type II / genetics
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology
  • Protein Kinase Inhibitors / pharmacology
  • Recombinant Fusion Proteins / physiology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / physiology*
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / physiology


  • Lipopolysaccharides
  • NF-kappa B
  • Peptide Fragments
  • Protein Kinase Inhibitors
  • Recombinant Fusion Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Dinoprostone