Lithium blocks the PKB and GSK3 dephosphorylation induced by ceramide through protein phosphatase-2A

Cell Signal. 2002 Jun;14(6):557-62. doi: 10.1016/s0898-6568(01)00282-0.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Lithium / pharmacology*
  • Neuroprotective Agents / pharmacology
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Wistar
  • Sphingosine / analogs & derivatives*
  • Sphingosine / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • N-acetylsphingosine
  • Neuroprotective Agents
  • Proto-Oncogene Proteins
  • Lithium
  • Glycogen Synthase Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Sphingosine