Hexadecylphosphocholine inhibits translocation of CTP:choline-phosphate cytidylyltransferase in Madin-Darby canine kidney cells.
The mechanism of the inhibition of phosphatidylcholine biosynthesis by the phospholipid analogue, hexadecylphosphocholine, was investigated in Madin-Darby canine kidney cells. In the presence of 50 mumol/liter hexadecylphosphocholine, there was a translocation of CTP:choline-phosphate cytidylyltransferase (EC 22.7.7.15) activity from the membranes to the cytosol of the cells. Since we recently demonstrated that hexadecylphosphocholine also inhibits protein kinase C in vitro, [methyl-3H]choline labeling experiments were repeated with phorbol ester-desensitized cells. In these cells the same inhibitory effect of hexadecylphosphocholine was measured. As a consequence of inhibition, the [methyl-3H]choline incorporation into the phosphocholine pool was increased time-dependently. In addition, there was no evidence for a difference between the choline uptake of control and hexadecylphosphocholine-treated cells. Likewise, the amount of diacylglycerol, a known activator of the translocation process, was not reduced. Finally, we showed that the inhibitory effect of hexadecylphosphocholine on CTP:choline-phosphate cytidylyltransferase translocation cannot be explained by the detergent properties of this phospholipid analogue. Therefore, we suggest a direct inhibitory effect of hexadecylphosphocholine on the translocation of CTP:choline-phosphate cytidylyltransferase.
Geilen
C C
CC
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Germany.
Wieder
T
T
Reutter
W
W
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D004075:Diglycerides / Q000378:metabolism; D004285:Dogs; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D010713:Phosphatidylcholines; D010767:Phosphorylcholine; C039128:miltefosine; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline; D013755:Tetradecanoylphorbol Acetate