Phorbol myristate acetate stimulates degradation of a structural analogue of platelet-activating factor to a neutral lipid in human leukemic K562 cells: relevance to the release of lipids.
In our attempt to investigate the mechanism of the release of platelet-activating factor (PAF) from cells, the erythroleukemic cell line K562 was preloaded with a radiolabeled PAF analogue having an ethylcarbamyl residue, 1-O-octadecyl-2-O-ethylcarbamyl-sn-glycero-3-phosphocholine (ethylcarbamyl-PAF), that is resistant to the hydrolytic action of PAF acetylhydrolase. Its extracellular release was monitored using an albumin back-extraction method, and its metabolic degradation was analyzed by TLC. Phorbol myristate acetate (PMA) was found to stimulate the release of two radioactive lipids, ethylcarbamyl-PAF itself and its metabolite, 1-O-octadecyl-2-ethylcarbamyl-sn-glycerol, whereas only ethylcarbamyl-PAF was released from the resting cells. The increased release of radioactive lipids in PMA-stimulated cells was suggested to be due to stimulated degradation of intracellular ethylcarbamyl-PAF into the cell-permeable metabolite. Thus K562 cells have much less capacity to release intact PAF-like lipid in comparison with its high ability to uptake exogenously added PAF analogues previously described by us and others.
Tsutsumi
Toshihiko
T
Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-cho, Nobeoka, Miyazaki 882-8508, Japan. t-tsutsumi@phoenix.ac.jp
Tokumura
Akira
A
Yamaguchi
Masaya
M
Kitazawa
Shikifumi
S
Tanigawara
Yusuke
Y
D001711:Biotransformation; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003470:Culture Media; D006801:Humans; D020014:K562 Cells; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D009636:Norbornanes; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry*; D012969:Sodium Fluoride / Q000494:pharmacology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology
D001952:Bridged-Ring Compounds; D003470:Culture Media; D008055:Lipids; D009636:Norbornanes; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D012969:Sodium Fluoride; D013755:Tetradecanoylphorbol Acetate