FEBS Letters | |
Differential effects of free and liposome‐associated 1‐O‐octadecyl‐2‐O‐methylglycerophosphocholine on protein kinase C | |
Edsall, Lisa C.2  Spiegel, Sarah2  Cuvillier, Olivier2  Janoff, Andrew S.1  Olah, Zoltan2  | |
[1] The Liposome Company, Princeton, NJ 08540, USA;Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 353 Basic Science Building, 3900 Reservoir Road NW, Washington, DC 20007, USA | |
关键词: Liposome; Protein kinase C; 1-O-Octadecyl-2-O-methylglycerophosphocholine; 12-O-Tetradecanoylphorbol 13-myristate; Apoptosis; Ac-DEVD-CHO; acetyl-Asp-Glu-Val-Asp-aldehyde; ara-C; 1-β-D-arabinofuranosylcytosine; ET-18-OCH3; 1-O-octadecyl-2-O-methylglycerophosphocholine; Chol; cholesterol; DOPC; dioleoylphosphatidylcholine; DOPE-GA; dioleoylphosphatidylcholine-glutaric acid; ELL-12; DOPC/Chol/DOPE-GA/ET-18-OCH3 (4:3:1:2); FBS; fetal bovine serum; PKC; protein kinase C; TPA; 12-O-tetradecanoylphorbol 13-myristate; | |
DOI : 10.1016/S0014-5793(99)00796-6 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Incorporation of ET-18-OCH3 into well-characterized liposomes known as ELL-12 has eliminated its gastrointestinal and hemolytic toxicity without loss of growth inhibiting activity. ET-18-OCH3, but not ELL-12, blunted the increase in membrane protein kinase C (PKC) activity induced by 12-O-tetradecanoylphorbol 13-myristate (TPA) and markedly reduced levels of PKCα in NIH 3T3 fibroblasts. Furthermore, prolonged treatment with ELL-12 neither inhibited TPA-induced translocations of PKCα and PKCδ to the particulate fraction nor caused down-regulation, and did not affect the cellular distribution of TPA-insensitive PKCζ. In Jurkat T cells, where ELL-12 markedly induced apoptosis that was blocked by an inhibitor of caspase-3-like activities, it had no effect on PKC activity or translocation induced by TPA. Thus, it seems unlikely that PKC is involved in the therapeutic effects of ELL-12.
【 授权许可】
Unknown
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