Modulation of CTP:phosphocholine cytidylyltransferase translocation by oleic acid and the antitumoral alkylphospholipid in HL-60 cells.
Short time effect of oleate and 1-O-alkyl-2-O-methyl-rac-glycero-3-phosphocholine (AMGPC) on choline incorporation into phosphatidylcholines were studied in HL-60 cells. The non lytic concentration of 50 microM oleate induced a three-fold increase in [3H]choline incorporation into phosphatidylcholine. This stimulation was accompanied by a translocation of the CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15) from cytosol to membranes. By contrast, the ether-lipid AMGPC inhibited [3H]choline incorporation into phosphatidylcholine by 60% at 10 microM. AMGPC had no effect on choline kinase or choline phosphotransferase activities. When AMGPC was added separately to an homogenate, a particulate or a cytosolic fraction, cytidylyltransferase inhibition was observed only in the homogenate. However on particulates recovered from homogenates treated with increasing concentrations of AMGPC, membranous cytidylyltransferase activity decreased dose-dependently. Thus AMGPC had no effect on cytidylyltransferase activity itself but inhibited its translocation from cytosol to membrane. At variance with the well-established positive effect on cytidylyltransferase translocation induced by fatty acids, this is the first demonstration that AMGPC can inhibit cytidylyltransferase translocation in cell-free system.
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Institut National de la Santé et de la Recherche Médicale, Unité 326, Toulouse, France.
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002474:Cell-Free System; D002794:Choline / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*
D000970:Antineoplastic Agents; D009829:Oleic Acids; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D019301:Oleic Acid; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline