Abstract
The biochemical mechanism of apoptosis induced by ceramide remains still unclear, although it has been reported that dephosphorylation of PKB at Ser-473 may be a key event. In this article, we show that C(2)-ceramide (N-acetyl-sphingosine) induces the dephosphorylation of both protein kinase B (PKB) and glycogen synthase kinase-3 (GSK3) in cerebellar granule cells (CGC). We also show that lithium protects against the apoptosis induced by C(2)-ceramide by blocking the dephosphorylation of both kinases. Since lithium inhibits in vivo the observed protein phosphatase-2A (PP2A) activation induced by ceramide, we hypothesise that the neuroprotective action of lithium may be due to the inhibition of the PP2A activation by apoptotic stimuli.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / enzymology*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Lithium / pharmacology*
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Neuroprotective Agents / pharmacology
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Phosphoprotein Phosphatases / metabolism*
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Phosphorylation
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Protein Phosphatase 2
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Rats, Wistar
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Sphingosine / analogs & derivatives*
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Sphingosine / antagonists & inhibitors*
Substances
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Enzyme Inhibitors
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N-acetylsphingosine
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Neuroprotective Agents
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Proto-Oncogene Proteins
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Lithium
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Glycogen Synthase Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Phosphoprotein Phosphatases
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Protein Phosphatase 2
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Sphingosine