Protein kinase C inhibitors and PAF stimulate phosphatidylserine synthesis in human leucocytes.
To study the regulation and turnover of phosphatidylserine (PtdSer) in human leucocytes, we investigated the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA), I-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3 or edelfosine), staurosporine and platelet activating factor (PAF) on [14C]serine incorporation into phospholipids. More than 80% of lipid radioactivity was in PtdSer. ET-18-OCH3 stimulated incorporation into PtdSer 5-fold, without increasing incorporation into other lipids. PAF stimulated PtdSer synthesis 3-fold after 1 h, while staurosporine stimulated the synthesis 2-fold after 3 h. TPA inhibited PtdSer synthesis. It abolished the ET-18-OCH3 stimulation, and reduced the staurosporine stimulation. ET-18-OCH3 and TPA did not significantly alter the incorporation of [14C]arachidonic acid into PtdSer, and did not increase PtdSer turnover judged from chase and stability experiments. The results demonstrate that PKC inhibitors and PAF induce increased incorporation of [14C]serine into PtdSer, while TPA inhibits stimulated PtdSer synthesis. This suggests that modulation of PtdSer synthesis may regulate PKC activity in PMN cells.
Bleivik
B
B
Department of Clinical Chemistry, University Hospital of Trondheim, Norway.
White
L R
LR
Bjerve
K S
KS
D000970:Antineoplastic Agents / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010718:Phosphatidylserines / Q000096:biosynthesis*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012694:Serine / Q000378:metabolism / Q000494:pharmacology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine; D012694:Serine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate