Phosphatidylcholine cycle: an intracellular signaling mechanism in the primordial human placenta.
The effects of 4 beta-phorbol-12-myristate-13-acetate (PMA) and 1,2-sn-dioctanoylglycerol (DOCG) on the rate of labeling of phosphatidylcholine (PC) with (32P)phosphate and the rate of formation of (3H)phosphatidylethanol (PET) from PC labeled with (3H)myristic acid were investigated in vitro in minced placentae obtained from first trimester human pregnancies. Maximally effective concentrations of PMA (1 microM) or DOCG (125-250 microM) stimulate PC-labeling with (32P)phosphate along different time courses: responses to DOCG and PMA require 30 and 60 min, respectively. The early response to DOCG is attended by a rapid accumulation of 32P)PCDOCG followed by a decline from the peak value in the second 30 min. The PMA effect is accompanied by increased rate of formation of (32P)phosphatidic acid (PA). Importantly, the effects of PMA and DOCG on PC-labeling are additive and PMA does not have any effect on the labeling of PCDOCG. These findings indicate that PMA stimulates degradation and the attendant turnover of PC, whereas a greater part of the DOCG-effect comes from the stimulation of PC synthesis de novo. Consistent with this notion is the finding that PMA enhances the PC-selective phospholipase D activity (measured by the formation of PET) 2.4-fold, whereas the effect of DOCG is smaller (1.4-1.8-fold) and not additive with that of PMA. The results provide evidence for the presence of functional PC-cycle in the primordial human placenta. The cycle can be triggered by a single addition of PMA and to a lesser extent by DOCG. The smaller effect of DOCG may be related to its short lifetime in the tissue, which is sufficient, however, to stimulate the activity of the regulatory enzyme (CTP: choline cytidylyl transferase) of PC synthesis. Since the effect of PMA on PC-labeling is diminished by protein kinase C inhibitors, this enzyme appears to be involved in the stimulation of PC-cycle by DAG and its analogs.
Tóth
M
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Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, Budapest, Hungary.
D004075:Diglycerides / Q000494:pharmacology; D005260:Female; D020404:Glycerophospholipids; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010920:Placenta / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D004075:Diglycerides; D020404:Glycerophospholipids; D009227:Myristic Acids; D010710:Phosphates; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; C051521:phosphatidylethanol; D019814:Myristic Acid; D014316:Tritium; C044295:1,2-dioctanoylglycerol; D013755:Tetradecanoylphorbol Acetate