Different dependence of lithium and valproate on PI3K/PKB pathway

• DOI: 10.1034/j.1399-5618.2002.40301.x
• Publication Date: 2003-03-11T04:49:50Z
• Authors: Alfonso Mora; Guadalupe Sabio; Juan C Alonso; Germán Soler; Francisco Centeno
• Keywords: Neurons; 0301 basic medicine; Enzyme Precursors; 0303 health sciences; Apoptosis; Lithium; Protein Serine-Threonine Kinases; Ceramides; Caspase Inhibitors; Rats; 3-Phosphoinositide-Dependent Protein Kinases; Enzyme Activation; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Neuroprotective Agents; Animals, Newborn; Antimanic Agents; Caspases; Cerebellum; Potassium; Animals; Rats, Wistar; Cells, Cultured

Objectives: Acute treatment with valproate (VPA) or lithium (Li + ) protects cerebellar granule cells (CGC) against apoptosis induced by low potassium (K (5 mM). As the protection VPA is absolutely dependent on insulin, in contrast to observed effects of Li , we decided study different role PI3K/PKB pathway neuroprotective both drugs. Methods: We have studied neuroprotection elicited cultures rat CGC. switching a medium concentration K adding C 2 ‐ceramide cultures. effect and viability regulation pathway. Results conclusions: Insulin also ‐induced CGC, probably through its interaction an insulin‐like growth factor receptor. Moreover, whereas ‐ceramide, cannot, due inhibition protein kinase B (PKB) caused this apoptotic stimulus. These results suggest that acting pathway; however, does not affect increase PKB activity insulin these cells. The independent transduction blocks caspase 3 activation neither nor affects activation.