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.
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.
Shimoke
K
K
Institute for Protein Research, Osaka University, Suita, Japan.
Yamada
M
M
Ikeuchi
T
T
Hatanaka
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D003470:Culture Media; D004789:Enzyme Activation / Q000187:drug effects; D008055:Lipids / Q000096:biosynthesis / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats
D003470:Culture Media; D008055:Lipids; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; C055525:phosphatidylinositol 3-phosphate; C494920:Akt1 protein, rat