Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate.
Effects of DL-palmitoylcarnitine (PC), an inhibitor of calciumactivated, phospholipid-dependent protein kinase (protein kinase C), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell differentiation were investigated in human promyelocytic leukemia cells (HL-60). TPA caused HL-60 cell adhesion concomitant with morphological changes, and an increase in acid phosphatase activity. The median effective concentration was 1 nM, which corresponded well to the dissociation constant of [3H]TPA binding to the cell extract. [3H]TPA binding to the cell extract was saturable and reversible. The maximal number of [3H]TPA-binding sites was 1.5 pmol/mg protein and a Hill coefficient was unity, indicating noncooperative interactions. PC, but neither palmitic acid nor DL-carnitine, inhibited the TPA-induced cell adhesion and morphological changes with the median inhibitory concentration of 1 microM, whereas a TPA-induced increase in acid phosphatase activity was not affected by 3 microM PC. Addition of PC 1 or 2 days after the addition of TPA was also effective in inhibiting the cell adhesion. Among various acylcarnitines, PC had the largest effect. [3H]TPA binding to the cell extract was not inhibited by PC at the concentration which was effective in inhibiting the TPA-induced cell adhesion. These results indicate that protein kinase C possibly mediates HL-60 cell differentiation induced by TPA.
D029742:Caenorhabditis elegans Proteins; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002352:Carrier Proteins; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004336:Drug Antagonism; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011956:Receptors, Cell Surface / Q000378:metabolism; D011955:Receptors, Drug; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D010704:Phorbols; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D010172:Palmitoylcarnitine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002331:Carnitine