Induction of cyclooxygenase-2 by overexpression of the human catalase gene in cerebral microvascular endothelial cells.
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.[1]References
- Induction of cyclooxygenase-2 by overexpression of the human catalase gene in cerebral microvascular endothelial cells. Fang, X., Moore, A.S., Nwankwo, J.O., Weintraub, L.N., Oberley, W.L., Snyder, D.G., Spector, A.A. J. Neurochem. (2000) [Pubmed]
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