REGULATION OF CYCLOOXYGENASE GENE-EXPRESSION IN RAT SMOOTH-MUSCLE CELLS BY CATALASE

We have studied, in detail, the effect of catalase, one of the natural ly occurring antioxidant enzymes, on the expression of cyclo-oxygenase (COX) mRNA and protein in rat aortic smooth muscle cells (RASMC). The activity of COX enzyme within the cells was also determined. Catalase either alone or in combination with interleukin-1 beta (IL-1 beta) en hanced mRNA and protein expression for cyclo-oxygenase 2 (COX-2) in a concentration-dependent manner. However, it did not affect the express ion of mRNA or protein for cyclo-oxygenase 1 (COX-1). The expression o f mRNA for COX-2 induced by catalase was blocked completely by actinom ycin D (ACT) or cycloheximide (CHX). In comparison, expression of mRNA for COX-2 stimulated by IL-1 beta was inhibited by actinomycin D, but not by cycloheximide. This suggests that induction of the synthesis o f mRNA for COX 2 by catalase and IL-1 beta involves different mechanis ms. In particular, the induction of mRNA for COX-2 by catalase require s on-going protein and RNA synthesis, but the induction following expo sure to IL-1 beta does not. The increase in expression of mRNA for COX -2 induced by catalase may be related to the ability of catalase to st imulate cyclic AMP response element (CRE) and NF-IL6 transcription fac tors, but not nuclear factor kappa B (NF-kappa B), for electrophoretic mobility shift assays (EMSA) showed that catalase enhanced nuclear fa ctor binding to cyclic AMP response element and NF-kappa B but not to NF-kappa B. Catalase exerted a biphasic effect on prostaglandin synthe sis. At low concentrations it enhanced prostaglandin production, but a t high concentrations it tended to inhibit it. These findings suggest that catalase has differential and multiple effects on COX expression and activity in rat aortic smooth muscle cells. (C) 1998 Elsevier Scie nce Inc.