Induction of cyclooxygenase-2 by overexpression of the human catalase gene in cerebral microvascular endothelial cells

J Neurochem. 2000 Aug;75(2):614-23. doi: 10.1046/j.1471-4159.2000.0750614.x.


Prostaglandin (PG) formation by the inducible (type 2) cyclooxygenase (COX-2) and reactive oxygen species (ROS) have been proposed to play important roles in cerebrovascular pathological processes. To explore the relationship between ROS and COX-2 expression, adenovirus (Ad) vectors containing cDNA for human antioxidant enzymes including catalase (AdCAT:), copper/zinc superoxide dismutase (AdCu/ZnSOD), and manganese superoxide dismutase (AdMnSOD) were transferred into murine cerebral microvascular endothelial cells. AdCAT: (100 multiplicity of infection) infection increased the content and enzymatic activity of cellular Cat threefold and decreased the intracellular peroxide level. The expression of COX-2 mRNA and protein in cell lysates was up-regulated, and the amount of PGE(2) formed from exogenous arachidonic acid increased following AdCAT: infection in a dose-dependent manner, paralleling the expression of COX-2 protein. The AdCAT:-induced increase in PGE(2) formation was inhibited by NS-398, a selective inhibitor of COX-2 enzymatic activity. AdCAT: infection did not change the expression of the constitutive (type 1) COX protein. Although AdCu/ZnSOD and AdMnSOD infection increased the expression of superoxide dismutase proteins, COX-2 expression was not induced. An in vitro nuclear transcription assay indicated that overexpression of the Cat gene increases the transcription of the COX-2 gene. Furthermore, the stability of COX-2 mRNA induced by lipopolysaccharide was increased after AdCAT: gene transfer. These results indicate that AdCAT: gene transfer induces the transcriptional activation of the COX-2 gene and increases COX-2 mRNA stability. Therefore, peroxide may have regulatory effect on COX-2 function in the cerebral microcirculation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Catalase / genetics*
  • Catalase / metabolism
  • Cells, Cultured
  • Cerebrovascular Circulation
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Enzyme Induction
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Mice
  • Microcirculation
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic
  • Transfection
  • beta-Galactosidase / genetics


  • Isoenzymes
  • Membrane Proteins
  • Reactive Oxygen Species
  • Arachidonic Acid
  • Catalase
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • beta-Galactosidase
  • Dinoprostone