Phorbol esters inhibit inositol phosphate and diacylglycerol formation in proliferating HL60 cells. Relationship to differentiation.
Phorbol 12-myristate 13-acetate (PMA) induces the differentiation of the human promyelocytic cell line, HL60, towards adherent macrophage-like cells within 2 days. We have examined the early effects of PMA on inositol phosphates and on diacylglycerol production, two second messengers derived from inositol lipids. In proliferating HL60 cells, PMA induced a time- and concentration-dependent decrease in inositol phosphate levels. Maximal effects were seen after 1 h at 10 nM PMA. PMA also induced the translocation of protein kinase C from the cytosol to the membrane. Comparison between the differentiating effects of several phorbol esters and of 1-oleoyl-2-acetylglycerol with their ability to inhibit inositol phosphate formation suggests that the two effects are correlated.
Geny
B
B
INSERM, Unité 204, Hopital Saint Louis, Paris, France.
LePeuch
C
C
Cost
H
H
Basset
M
M
Cockcroft
S
S
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004075:Diglycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005989:Glycerides / Q000096:biosynthesis*; D006801:Humans; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute; D010703:Phorbol Esters / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D010703:Phorbol Esters; D013403:Sugar Phosphates; D013755:Tetradecanoylphorbol Acetate