Cyclooxygenases are key enzymes in the arachidonic acid metabolism. Their unstable intermediate, prostaglandin H2, is further metabolized to bioactive lipids by various downstream enzymes. In this study, utilizing short hairpin RNAs, we prepared a cell line of human cervix carcinoma with stable down-regulated cyclooxygenase-1 (COX-1) to assess the impact of COX-1 reduction on the downstream enzymes. We found a significant microsomal prostaglandin E synthase-1 (mPGES-1) suppression. In addition, mRNA expression of multidrug resistance protein 4 (MRP4, ABCC4), supposed to take part in antiviral and anticancer drug transport from cells, was up-regulated after COX-1 down-regulation. Our findings indicate that mPGES-1, believed to be coexpressed preferentially with cyclooxygenase-2, may be coupled to COX-1. ABCC4 up-regulation further supports the assumption of its involvement in prostanoid transport.
Cyclooxygenase Prostaglandin E synthase mPGES-1 Multidrug resistance protein ABCC4 shRNA
Microsomal prostaglandin E synthase
Multidrug resistance protein 4
ATP-binding cassette, sub-family C, member 4
Nonsteroidal anti-inflammatory drugs
Prostaglandin E synthase
Cytosolic prostaglandin E synthase
Short hairpin RNA
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This study was supported by the grant NR8760-4/2006 from the Ministry of Health, Czech Republic and GENERI BIOTECH s.r.o.
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