Relationship between membrane sterol composition and responsiveness to 12-O-tetradecanoylphorbol 13-acetate in HL-60 human promyelocytic leukaemia cell lines.
We have examined the sterol composition and metabolism of promyelocytic leukaemia cell lines (HL-60) after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). A variant cell line (Blast II cells) which is resistant to TPA was used as control. Analysis of the sterols of TPA-sensitive cells radiolabelled with [3H]leucine, [14C]acetate or [14C]pyruvate showed a high incorporation into cholesterol and a low incorporation in lanosterol + dihydrolanosterol. The inverse relationship was observed in TPA-resistant cells. Experiments with other cellular variants representing TPA-sensitive and TPA-resistant classes gave similar results. Analysis of the cellular sterol composition by gas chromatography confirmed that TPA-resistant cells are particularly rich in lanosterol/dihydrolanosterol. TPA treatment enhanced the incorporation of [14C]pyruvate into the sterol fraction of both cell types. This was accompanied by an alteration of incorporation into several lipids, particularly phospholipids. Pulse-chase studies with [14C]acetate revealed that TPA induced the release of radioactive lipids into the medium from HL-60 and Blast II cells. However this treatment released phospholipids from the TPA-sensitive cells and sterols and fatty acids from the TPA-resistant cells. We conclude that the sterol composition can regulate specific biochemical processes in the membrane and can be considered as a factor that plays a role in the responsiveness of HL-60 cells to TPA.
Malvoisin
E
E
Unité de Virologie fondamentale et appliquée, INSERM U.51, CNRS U.613, Lyon, France.
Wild
F
F
Zwingelstein
G
G
D000085:Acetates / Q000378:metabolism; D002250:Carbon Radioisotopes; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007810:Lanosterol / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D050356:Lipid Metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013261:Sterols / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000085:Acetates; D002250:Carbon Radioisotopes; D011773:Pyruvates; D013261:Sterols; D014316:Tritium; D007810:Lanosterol; D019289:Pyruvic Acid; D002784:Cholesterol; D007930:Leucine; D013755:Tetradecanoylphorbol Acetate