Synthetic lipid products of PI3‐kinase which are added to culture medium prevent low K+‐induced apoptosis of cerebellar granule neurons via Akt kinase activation

FEBS Letters

Yamada, Masashi¹  Ikeuchi, Toshihiko¹  Shimoke, Koji¹  Hatanaka, Hiroshi¹ 

[1] Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

关键词: Akt kinase;    Apoptosis;    Phosphatidylinositol 3-kinase;    Phosphatidylinositol 3;    4-bisphosphate;    Phosphatidylinositol 3;    4;    5-trisphosphate;    Survival signal;    PI3-K;    phosphatidylinositol 3-kinase;    HK+;    high potassium;    LK+;    low potassium;    BDNF;    brain-derived neurotrophic factor;    diC16;    dipalmitoyl;    MEM;    minimum essential medium;    MTT;    3-(4;    5-dimethyl-2-thiazolyl)-2;    5-diphenyl-2H-tetrazolium bromide;    PDK1;    phosphoinositide-dependent kinase-1;    PH;    pleckstrin homology;    PKB;    protein kinase B;    p70S6K;    p70 ribosomal S6 kinase;    PtdIns-3-P;    phosphatidylinositol 3-monophosphate;    PtdIns-3;    4-P2;    phosphatidylinositol 3;    4-diphosphate;    PtdIns-3;    4;    5-P3;    phosphatidylinositol 3;    4;    5-triphosphate;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(98)01235-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To examine which lipid product of phosphatidylinositol 3-kinase (PI3-K) is essential for the survival-promoting pathway in cultured cerebellar granule neurons, three synthetic derivatives of lipid products of PI3-K were added to culture medium containing a low concentration (5 mM) of potassium (LK⁺) which induces apoptotic cell death. We found that dipalmitoylphosphatidylinositol 3,4-bisphosphate and dipalmitoylphosphatidylinositol 3,4,5-trisphosphate, but not dipalmitoylphosphatidylinositol 3-monophosphate, effectively blocked the LK⁺-induced apoptosis. These two synthetic phospholipids increased Akt activity but not that of PI3-K. These findings demonstrated that specific lipid products of PI3-K which are added to culture medium activate Akt/PKB without modulating PI3-K itself, and as a result prevent neuronal cell death in cerebellar granule neurons.

【 授权许可】

Unknown