title: Protein kinase C is not involved in cholesterol-induced resistance to synthetic ether lipids.
abstract: The possible role of protein kinase C in cholesterol-induced resistance to ether lipids was investigated. The enrichment of HL60 cells in cholesterol (CHOL) (HL60-CHOL) resulted in a significant increase in the ID50 values for 1-octadecyl-2-methyl-rac-glycero- 3-phosphocholine (ET-18-OMe) (3.75 +/- 0.7 microM and 6.69 +/- 0.5 microM for HL60 and HL60-CHOL, respectively). In the same conditions, HL60 and HL60-CHOL cells showed comparable levels of both cytosolic and membrane-associated protein kinase C activity. Phorbol ester (PMA) stimulation induced protein kinase C to translocate from the cytosol to the plasma membrane in both cell types and with similar kinetics (272 +/- 32% and 299 +/- 41% increase in HL60 and HL60-CHOL, respectively after 100 ng/ml PMA for 10 min). Pretreatment of the two cell types with 50 microM ET-18-OMe resulted in comparable levels of PKC inhibition after phorbol ester stimulation. These results suggested that alterations in plasma membrane lipid composition induced by CHOL do not result in major changes in protein kinase C activity. Thus, protein kinase C does not appear to be involved in cholesterol-induced resistant phenotype in HL60 cells.
authors.affiliation: Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Diomede
authors.forename: M
authors.initials: M
authors.lastname: Salmona
authors.forename: G
authors.initials: G
authors.lastname: Lamorte
authors.forename: B
authors.initials: B
authors.lastname: Piovani
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D008563:Membrane Lipids; D010703:Phorbol Esters; D010742:Phospholipid Ethers; D002784:Cholesterol; D011493:Protein Kinase C