Differential effects of free and liposome‐associated 1‐O‐octadecyl‐2‐O‐methylglycerophosphocholine on protein kinase C

FEBS Letters

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