Abstract

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.

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