Opposite Effect of Phorbol Ester PMA on PTGS2 and PGDH mRNA Expression in Human Chorion Trophoblast Cells

Abstract

Prostaglandins (PGs) induce the mechanism of labor in humans. The enzymes responsible for PG synthesis and metabolism are prostaglandin-endoperoxide synthase 2 (PTGS2) and 15-hydroxyprostaglandin dehydrogenase (PGDH). In human chorion trophoblast cells, calcium ionophore A23187 upregulates PTGS2 and downregulates PGDH protein and mRNA. The authors hypothesize that this regulation requires activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs). Human chorion trophoblasts were incubated with A23187 or phorbol 12-myristate 13-acetate (PMA) in the absence or presence of inhibitors of PKC, c-Jun N-terminal kinase, p38, and MEK1/2. PTGS2 and PGDH mRNA were measured by real-time reverse-transcription polymerase chain reaction. PMA upregulated PTGS2 and downregulated PGDH. The PMA effect was reversed by the inhibition of PKC. The p38 inhibitor reduced the stimulatory effect of PMA and A23187 on PTGS2. MEK1/2 inhibitor reduced the effect of PMA on PTGS2. All MAPK inhibitors failed to reverse the effect of either A23187 or PMA on PGDH. The authors conclude that upon stimulation with the same upstream signals, different downstream intracellular pathways regulate PTGS2 and PGDH mRNA expression.

Prostaglandin dehydrogenase (PGDH) in granulosa cells of primate periovulatory follicles is regulated by the ovulatory gonadotropin surge via multiple G proteins

“…For example, cAMP generally stimulates PGDH expression, but cAMP decreased PGDH expression and activity in human trophoblast cells (Lennon et al 1999). Though PMA generally increases PGDH expression (Tai et al 2006), the ability of PMA to decrease PGDH expression has been reported (Casciani et al 2008). These examples provide precedent for the regulation of PGDH observed in the present study, where cAMP/Epac activation increased, and PLC/PKC activity decreased, PGDH mRNA, protein, and activity.…”

Polymer Surface Interacts with Calcium in Aqueous Media to Induce Stem Cell Assembly

“…After seeding, MSCs attach and spread on PU films. Local calcium near the leading edge of the cell can activate cell migration while the calcium influx can stimulate NF‐κB pathway and PTGS2 expression . The NF‐κB pathway has been reported to modulate the aggregate formation of neural stem cells .…”

Fetal membrane at the feto-maternal interface: An underappreciated and understudied intrauterine tissue

“…[2,17,20] Traditionally, it is known that fetal membranes produce cyclooxygenase-2 and prostaglandins that contribute to membrane weakening and rupture at term. [59][60][61][62][63][64] Recent studies suggest that fetal membranes from both humans and mice undergo a reactive oxygen species induced (due to intrauterine oxidative stress at term), telomere-dependent, activation of p38 mitogen-activated protein kinase (p38MAPK). [24,31,[65][66][67][68] p38MAPK is a stress signaler that can contribute to various cell fates.…”