• Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells.

Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells.

Journal of cellular and molecular medicine (2011-08-23)
Li Chen, Suren R Sooranna, Kaiyu Lei, Mandeep Kandola, Phillip R Bennett, Zhiqing Liang, Dimitri Grammatopoulos, Mark R Johnson

Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI(2) , acting via cAMP/PKA, was found to increase contraction-associated protein expression in myometrial cells and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and further studies confirmed that this was associated with COX-2 protein synthesis and activity (increased PGE(2) and PGI(2) in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP-effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP-effector PDZ-GEF(1-2) , without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX-2 expression and that PGE(2) acts through EP-2 to activate MAPK and increase COX-2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.

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Product Description

Monoclonal Anti-RAPGEF2 antibody produced in mouse, clone 1E8, purified immunoglobulin, buffered aqueous solution
GeneJuice® Transfection Reagent, Non-lipid based chemical transfection reagent optimized for maximum transfection efficiency, ease-of-use, and minimal cytotoxicity on a wide variety of mammalian cells.
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture
Sodium thiophosphate tribasic hydrate, ≥90%