COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells

  • Hana Radilova
  • Antonin Libra
  • Sarka Holasova
  • Martina Safarova
  • Alena Viskova
  • Filip Kunc
  • Martin Buncek
Article

Abstract

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.

Keywords

Cyclooxygenase Prostaglandin E synthase mPGES-1 Multidrug resistance protein ABCC4 shRNA 

Abbreviations

COX

Cyclooxygenase

mPGES

Microsomal prostaglandin E synthase

MRP4

Multidrug resistance protein 4

ABCC4

ATP-binding cassette, sub-family C, member 4

NSAIDs

Nonsteroidal anti-inflammatory drugs

AA

Arachidonic acid

PG

Prostaglandin

PGES

Prostaglandin E synthase

cPGES

Cytosolic prostaglandin E synthase

shRNA

Short hairpin RNA

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Hana Radilova
    • 1
    • 2
  • Antonin Libra
    • 1
  • Sarka Holasova
    • 1
  • Martina Safarova
    • 1
  • Alena Viskova
    • 1
    • 3
  • Filip Kunc
    • 1
    • 3
  • Martin Buncek
    • 1
  1. 1.GENERI BIOTECH s.r.oHradec KraloveCzech Republic
  2. 2.Department of Biochemical Sciences, Faculty of Pharmacy in Hradec KraloveCharles University in PraguePragueCzech Republic
  3. 3.Department of Medical Biology and Genetics, Faculty of Medicine in Hradec KraloveCharles University in PraguePragueCzech Republic

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